Research progress in regulating intestinal flora structure and repairing intestinal mucosal barrier damage through Tongfu method / 国际中医中药杂志

The intestinal flora and gut barrier function are of great significance for gut function and human health. When the intestinal flora is disrupted and the gut barrier structure is disrupted, it can lead to bacterial translocation, endotoxin influx into the bloodstream, and the production of pro-inflammatory factors, leading to various tissue damage in the body. Tongfu method in TCM can affect the intestinal environment by regulating intestinal permeability and immune response, restoring normal intestinal movement, and regulating the structure and metabolites of intestinal flora, thereby maintaining intestinal homeostasis and body health. The research on regulating intestinal flora and improving intestinal barrier function by Tongfu method can provide reference for further research on the relationship between TCM and intestinal microecology, and provide ideas for clinical treatment.

Effects of berberine hydrochloride tablets combined with compound glutamine on intestinal mucosal barrier function in patients with ulcerative colitis / 天津医药

Objective To investigate the effect of berberine hydrochloride tablets combined with compound glutamine in treating ulcerative colitis(UC).Methods One hundred and two patients with UC admitted to our hospital were collected and grouped into two groups according to the random number table.Fifty-one patients in the control group were given conventional treatment+compound glutamine,and 51 patients in the experimental group were given berberine hydrochloride tablets based on the control group.Both groups were treated for 8 weeks.The efficacy,modified Mayo score,intestinal mucosal barrier function,soluble late glycation end product receptor(sRAGE),interleukin-17(IL-17),IL-6 and incidence of untoward reactions were compared between the two groups.Results The total effective rate of the experimental group was higher than that of the control group(92.2%vs.76.5%,P＜0.05).After treatment,scores of defecation frequency,blood in stool,endoscopic findings,physician's overall evaluation,diamine oxidase(DAO),D-lactic acid,endotoxin,sRAGE,IL-17 and IL-6 were lower in both groups than those before treatment(P＜0.05),and the research group was lower than the control group(P＜0.05).There was no significant difference in the total incidence of untoward reactions between the experimental group and the control group(P＞0.05).Conclusion Berberine hydrochloride tablets combined with compound glutamine are effective in treating UC,which can reduce the activity of UC,improve the intestinal mucosal barrier function,regulate serum sRAGE,IL-17 and IL-6 levels,without increasing adverse reactions.

Effect of oxymatrine on Cryptosporidium parvum infection in mice based on the HMGB1-TLR2/TLR4-NF-κB pathway / 中国血吸虫病防治杂志

Objective To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice. Methods Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay. Results HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05). Conclusions C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.

Optimization of the azomethane oxide and dextran sodium sulfate model of colitis-associated colon cancer and changes in the intestinal microbiota / 中国实验动物学报

Objective To optimize the method of combining azomethane oxide(AOM)and dextran sodium sulfate(DSS)to create a colitis-associated colon cancer(CAC)model,and to explore the pathogenesis of the intestinal flora in CAC.Methods Model groups A and B were established by one and two injections of AOM,respectively,combined with free drinking of DSS,and a normal control group was injected intraperitoneally with normal saline combined with purified water(n=10 mice per group).The better modeling scheme was selected by comprehensive evaluation of the disease activity index score,colon length,tumor rate,and mortality.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and tumor markers CA199,CEA,and CA724 were detected by enzyme-linked immunosorbent assay.Colon lesions were evaluated by hematoxylin and eosin(HE)staining.Changes in the intestinal microbiota in CAC mice were detected by 16S rDNA high-throughput gene sequencing analysis of mouse feces.Results Both single and enhanced AOM injections combined with DSS induced CAC mice;however,colon growths were larger,more closely arranged,and their morphological size was more consistent in group B compared with group A,with a tumor-formation rate of 100％.IL-6 levels were increased in the model group compared with the normal group(P＜0.05).TNF-α levels were increased in the model group compared with the normal group(P＞0.05).The CA199 and CEA levels were also significantly increased(P＜0.05),but CA724 levels were not.Infiltration of inflammatory cells in the colon detected by HE pathology was accompanied by high-grade intraepithelial tumor-like changes on the surface of the lumen.The diversity and abundance of intestinal bacteria were decreased in CAC mice compared with normal mice:phyla Verrucomicrobiota and Actinobacteriota were significantly increased(P＜0.05),Bacteroidota and Campilobacterota were significantly decreased(P＜0.05).Akkermansia,Prevotellaceae,Ruminococcus,and Bifidobacterium were significantly increased(P＜0.05),and Roseburia,Rikenellaceae_RC9_gut_group,Anaeroplasma,and Muribaculaceae were significantly decreased(P＜0.05).Conclusions Two injections of AOM combined with 1.5％(1.5 g/100 mL)DSS induced CAC model mice with a high colon-tumorigenesis rate,uniform tumor morphology,and low mortality,and may thus be the preferred modeling scheme for pharmacodynamic experiments.Disorders or dysfunction of the intestinal flora may lead to increased permeability,loss of intestinal mucosal barrier function,and the release of enterogenic endotoxins,Resultsing in a sustained inflammatory response,as an indirect or direct cause of CAC pathogenesis.

Construction of small intestinal organoid model in insulin-resistant mice and protective effect of flavanomarein on intestinal mucosal barrier in this model / 中国药理学与毒理学杂志

OBJECTIVE To construct an insulin-resistant(IR)small intestinal organoid model of mice and study the protective effect of flavanomarein(FM)on the intestinal mucosal barrier in the model.METHODS ①Small intestinal organoid models of C57BL/6J and db/db of mice were constructed.The expressions of Ki-67,E-cadherin(E-cad),lysozyme(Lyz)and mucin-2(Muc-2)in small intestinal organ-oids were detected by 3D immunofluorescence.RT-qPCR was used to detect the expressions of fibro-nectin(Fn),glucagon-like peptide-1(GLP-1)and peotide YY(PYY)mRNA while Western blotting was used to detect the expressions of Fn,GLP-1 and PYY protein.The Lyz secretion level was detected by ELISA.② Small intestinal organoids were divided into five groups:C57BL/6J mice 'small intestinal organ-oids as the normal control group,db/db mice' intestinal organoids as the IR model group,db/db mice small intestinal organoids with flavanomarein 25,50 and 100 μmol·L-1 intervention for 48 h as IR model+ FM groups.RT-qPCR was used to detect the expression of Lyz mRNA while Western blotting was used to detect the expression of Lyz protein.RESULTS ① On the 6th day of small intestinal organoid culture,a ring structure with a clear luminal structure was formed and an IR mouse small intestinal organoid model was established.3D Immunofluorescence detection showed that the established small intestinal organoids all expressed Ki-67,E-cad,Lyz and MUC-2.Compared with the normal control group,the expres-sion of Fn mRNA in the IR model group was significantly increased(P<0.05)while the expressions of GLP-1 and PYY mRNA were significantly decreased(P<0.05).Compared with the normal control group,the expression of Fn protein in the IR model group was significantly decreased(P<0.05)while the expressions of GLP-1 and PYY protein were significantly increased(P<0.05).ELISA results showed that compared with the normal control group,the secretion levels of Lyz in the IR model group were signifi-cantly decreased(P<0.01).② RT-qPCR results showed that compared with the normal control group,the expression of Lyz mRNA in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz mRNA in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).Western blotting results showed that compared with the normal control group,the expression of Lyz protein in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz protein in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).CONCLUSION The constructed IR mouse small intestinal organoid model provides a more complete in vitro research model for exploring the pathophysiological mechanism by which drug interventions help repair the intestinal mucosal barrier.FM may maintain the intestinal mucosal barrier by reversing the decrease in Lyz expression levels in IR mice,thereby improving IR.

Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis / 中国中药杂志

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor / 中西医结合学报

OBJECTIVE@#This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).@*METHODS@#Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.@*RESULTS@#Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.@*CONCLUSION@#Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

Effects of Ganbao capsules on intestinal mucosal barrier and gut microbiota in rats with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To study the effects of Ganbao capsules on intestinal mucosal barrier and gut microbiota in rats with non-alcoholic fatty liver disease （NAFLD）， and to explore its mechanism of prevention and treatment of NAFLD. METHODS Eight of 26 SD rats were randomly selected as blank group and fed with ordinary diet， and the remaining 18 rats were fed with high diet to establish NAFLD model （2 for modeling inspection）； after successful modeling， they were divided into model group and Ganbao group， with 8 rats in each group. Ganbao group were given Ganbao capsules solution （1 440 mg/kg） intragastrically， and the blank group and model group were given the constant volume of distilled water intragastrically， once a day， for consecutive 5 weeks. The contents of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and triglyceride （TG） in serum of rats were detected by automatic analyzer； the contents of lipopolysaccharide， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum of rats were detected by enzyme-linked immunosorbent assay. The pathological morphology of liver and ileum tissues were observed by HE staining， the expressions of Occludin and zonula occludens-1 （ZO-1） were detected by immunohistochemistry method， and the intestinal flora were detected by 16S ribosomal RNA gene sequencing technology. RESULTS Compared with the model group， the serum contents of ALT， AST， TG， lipopolysaccharide， TNF-α， IL-6 and IL-1β in Ganbao group were decreased significantly （P＜0.01）， the pathological changes of liver and ileum tissues were improved 262 significantly， and the expressions of Occludin and ZO-1 were increased significantly （P＜0.01）. Intestinal microbiotaanalysis revealed that compared with the model group， Ganbao capsules could recover the abundance and diversity of the gut E-mail：hdf8833@126.com microbiota in rats. At the phylum level， Ganbao capsules could significantly increase the relative abundance of Bacteroidetes， and significantly reduce the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes （P＜0.01）. At the genus level， Ganbao capsules could significantly increase the relative abundance of Lactobacillus， Blautia， Bacteroides and Akkermansia， and significantly reduce the relative abundance of Prevotella， Turicibacter， Weissella， SMB53 and Desulfovibrio （P＜0.05 or P＜0.01）. There were different species among the gut microbiota of rats in each group. CONCLUSIONS Ganbao capsules may improve NAFLD by protecting intestinal mucosal barrier function and regulating gut probiotics/harmful bacteria structure.

Renshen Baidusan Protects Mucosal Barrier in Ulcerative Colitis via AMPK/ULK1 Autophagy Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of Renshen Baidusan in regulating adenylate-activated protein kinase （AMPK）/Unc-51-like kinase 1 （ULK1） autophagy pathway to inhibit mucosal barrier damage in the mouse model of ulcerative colitis （UC）. MethodSixty SD rats were randomized into normal， model， sulfasalazine enteric-coated tablets （0.312 5 g·kg-1， western medicine）， and high-， medium-， and low-dose （31.2， 15.6， 7.8 g·kg-1， respectively） Renshen Baidusan groups. The UC model was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）/50% ethanol. The drugs were administrated by gavage for 2 weeks， and then the histopathological changes of the colon were examined. Real-time quantitative polymerase chain reaction was conducted to measure the mRNA level of AMP-activated protein kinase subunit alpha （AMPKα）. Western blot was employed to determine the protein levels of closure protein （Occludin）， compact linking protein-2 （Claudin-2）， autophagy marker p62， microtubule-associated protein 1 light chain 3B （LC3B）， phosphorylated AMPK （p-AMPK）， and phosphorylated ULK1 （p-ULK1）. ResultCompared with the normal group， the model group showed increased colon injury score （P<0.05）， down-regulated mRNA level of AMPKα （P<0.05） and protein levels of p-AMPK， p-ULK1， and Occludin， decreased LC3Ⅱ/Ⅰ ratio （P<0.05）， and up-regulated protein levels of p62 and Claudin-2 （P<0.05）. Compared with the model group， all the doses of Renshen Baidusan lowered the colon injury score， up-regulated the mRNA level of AMPKα and the protein levels of p-AMPK， p-ULK1， and Occluding， increased LC3Ⅱ/Ⅰ ratio， and down-regulated the protein levels of p62 and Claudin-2. Moreover， the medium-dose group showed a significant intervention effect （P<0.05）. ConclusionRenshen Baidusan can protect the intestinal mucosal barrier from damage， and the medium dose showed the best efficacy. It may activate the AMPK/ULK1 pathway to accelerate the transformation of LC3Ⅰ to LC3Ⅱ and promote the degradation of p62， so as to improve the function of Occludin and Claudin-2 and repair the mechanical damage of the intestinal barrier.

Protective effect of fructooligosaccharides on intestinal mucosal barrier in mice with ulcerative colitis / 中国小儿急救医学

Objective:To investigate the protective effect of water-soluble dietary fiber fructooligosaccharides(FOS) on intestinal mucosal barrier in mice with ulcerative colitis(UC), and to find a new drug option for the treatment of patients with UC.Methods:This study used 4% dextran sodium sulfate(DSS)to induce a 7-day UC mouse model.Male C57BL/6 mice aged 6-8 weeks were randomly divided into three groups: the control group drank distilled water; The model group was given 4% DSS; The oligofructose group was administered 20 mg/mL FOS by gavage simultaneously with DSS induction.The body weight, fecal characteristics, and fecal blood status of mice daily, and the disease activity index(DAI)score were monitored.After the experiment, HE staining was used to observe the pathological changes in the colon tissue of mice.Real time fluorescence quantitative PCR, Western Blot, and immunofluorescence staining were used to detect the expression levels of tight junction proteins ZO-1, Claudin-1, and Occludin in the intestines of each group of mice.Results:Compared with control group, the weight of mice decreased and the DAI score increased in model group( P<0.05). However, the weight of mice in FOS group was higher than that in model group, and the DAI score was lower than that in model group ( P<0.05). Compared with control group, the colon length of mice in model group was shortened[(7.52±0.41)cm vs.(5.48±0.19)cm], and the histopathological score was increased (0.53±0.38 vs.3.51±0.18). However, the colon length of mice in FOS group[(6.82±0.63)cm] was longer than that in model group, and the hispathological score(2.33±0.63) was lower than that in model group.All the differences were statistically significant ( P<0.05). The expression levels of ZO-1, Claudin-1, Occludin protein and its mRNA levels in model group were lower than those in control group ( P<0.05). However, those of FOS group were higher than those in model group ( P<0.05). Conclusion:FOS could alleviate the symptoms of weight loss in UC mice, reduce their DAI score, improve inflammation of colon tissue, upregulate the expression of tight junction proteins ZO-1, Claudin-1, and Occludin, and protect the intestinal mucosal barrier.

Effect of Huangqintang on Intestinal Flora in Mice with Ulcerative Colitis and Its Protective Mechanism on Intestinal Mucosal Barrier / 中国实验方剂学杂志

ObjectiveTo evaluate the pharmacodynamic effect of Huangqintang （HQT） on ulcerative colitis （UC） model mice and investigate its protective effect against UC by regulating intestinal flora. MethodMale Balb/c mice were randomly divided into control group，model group， high-， medium-， and low-dose HQT groups （20， 10， 5 g·kg-1）， flora interference group， flora interference model group， and flora interference-drug treatment group （HQT， 20 g·kg-1）. The flora interference model was constructed through intragastric administration of antibiotics （200 mg·kg-1 bacitracin and 200 mg·kg-1 vancomycin） for 8 d， and the UC model was constructed by allowing mice with free access to 3% dextran sulfate sodium （DSS） solution for 7 d. HQT was administered for 7 d. After the experiments， the mice were sacrificed， and blood， colon， and feces were collected. Hematoxylin-eosin （HE） staining was performed to observe the colonic lesions. The serum levels of interleukin （IL）-4， IL-6， IL-10， and tumor necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of Claudin1， MUC1， Occludin， and zonula occludens-1（ZO-1） in colon tissues was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The fecal DNA of mice was extracted and analyzed by high-throughput sequencing. ResultCompared with the normal group， the model group showed increased serum content of IL-4， IL-6， and TNF-α （P<0.05， P<0.01） and decreased IL-10 （P<0.05）. Compared with the model group， the HQT groups displayed decreased serum levels of IL-4， IL-6， and TNF-α （P<0.05， P<0.01）， increased IL-10 content （P<0.01）， increased mRNA and protein expression levels of Claudin1， MUC1， Occludin， and ZO-1 （P<0.05， P<0.01）. After flora interference， the diversity and abundance of intestinal bacteria decreased. To be specific， Proteobacteria increased （P<0.01）， and Firmicutes and Bacteroidetes decreased （P<0.01）. After UC induction by DSS， Bacteroidetes and Tenericutes decreased （P<0.05）. The high-， medium-， and low-dose HQT groups showed increased Bacteroidetes and Tenericutes （P<0.05， P<0.01） and decreased Firmicutes （P<0.05）. Additionally， the abundance of Lactobacillus， Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Helicobacteris was positively proportional to the dose of HQT. ConclusionHQT can inhibit the inflammatory response of UC mice， restore the imbalance of intestinal flora， and repair the damaged intestinal mucosal barrier.

Therapeutic effect of probiotics combined with ornithine aspartate on patients with liver cirrhosis complicated with hepatic encephalopathy / 中国综合临床

Objective:To explore the safety and therapeutic effect of probiotics combined with ornithine aspartate on patients with liver cirrhosis complicated by hepatic encephalopathy.Methods:72 patients with hepatic encephalopathy hospitalized in the Affiliated Hospital of North China University of Technology from January 2017 to December 2021 were randomly. According to the principle of comparability between groups in terms of gender and age, the group was divided into an observation group (36 cases) and a control group (36 cases) using a random number table method. The control group was treated with ornithine aspartate, while the case group was treated with probiotics combined with ornithine aspartate. The curative effect of the two groups of patients and the changes of serum inflammatory factors, intestinal flora and intestinal mucosal barrier function were observed.Results:The total effective rate of the case group was higher than that of the control group [97.22%(35/36) vs 83.33%(30/36)], The difference between groups is statistically significant (χ 2=2.53, P=0.112). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood ammonia, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF) in the two groups-α (TNF-α)、C-reactive protein (CRP), enterobacter, enterococcus content, endotoxin, D-lactic acid, diamine oxidase, and digital connection test (NCT) time were lower than before treatment [(-130.89±31.67) U/L vs (-98.64±43.41) U/L,(-137.81±31.92) U/L vs (-79.58±45.42) U/L, (-57.13±21.07) μmol/L vs (-45.92±18.11) μmol/L,(-164.06±19.30) μmol/L vs (-148.98±12.97) μmol/L, (-5.35±2.30) ng/L vs (2.18±2.77) ng/L,(-5.51±2.07) μmol/L vs (-3.72±1.50) ng/L, (-12.60±3.65) ng/L比(-7.97±5.86) ng/L, (-45.95±20.34) mg/L vs (-21.14±19.09) mg/L, (-2.70±1.53) vs (-1.31±2.47), (-2.50±1.26) vs (-1.39±1.97),(-0.32±0.09) EU/ml vs (-0.19±0.09) EU/ml, (-47.58±18.52) nmol/L vs (-32.31±22.21) nmol/L,(-3.44±1.06) U/ml vs (-1.86±1.30) U/ml, (-31.75±10.09) s vs (-14.58±10.10) s] and the scores of bifidobacterium, lactobacillus, and digital sign test (DST) were higher than before treatment [(2.77±1.76) vs (1.13±2.06), (3.23±1.61) vs (1.06±2.31), (32.58±5.72) vs (16.33±6.16)]. After treatment, ALT, AST, TBIL, blood ammonia, IL-6, IL-8, TNF in the case group-α, CRP, Enterobacter, Enterococcus content, endotoxin, D-lactic acid, diamine oxidase, NCT time were lower than those in the control group, and bifidobacterium, lactobacillus, DST scores were higher than those in the control group, with statistically significant differences(t-values of 3.60, 6.29, 2.42, 3.89, 5.28, 4.21, 4.03, 5.34, 2.87, 2.86, 6.11, 3.17, 5.63, 7.21, 3.61, 4.64 and 11.59. P-values of 0.001, <0.001, 0.018, <0.001, <0.001, <0.001, <0.001, <0.001, 0.005, 0.006, <0.001, 0.002, <0.001, <0.001, 0.001, <0.001, and <0.001). Conclusions:Micro-ecological preparation combined with ornithine aspartate has a significant therapeutic effect on patients with hepatic encephalopathy, which can significantly improve liver function and cognitive function of patients, reduce blood ammonia level, inhibit inflammatory reaction, improve intestinal flora and intestinal mucosal barrier function, with good safety, and is worthy of clinical promotion.

Dachaihu decoction protects intestinal mucosal barrier in severe heat stroke rats by inhibiting Toll-like receptor 4/nuclear factor-κB signaling pathway / 中国中西医结合急救杂志

Objective To explore the effect of Dachaihu decoction on the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)signaling pathway and gastrointestinal mucosal barrier in rats with severe heat stroke.Methods Sixty SPF grade Sprague-Dawley(SD)male rats were divided into normal control group,model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group of 15 rats in each group.The heat stroke model was replicated in the rats at temperature(40.5±0.5)℃and humidity(65.0±2.0)%;the normal control group was not treated.From 6 hours after mold making,drug intervention was carried out in the Dachaihu decoction high dose group and the Dachaihu decoction standard dose group of 3.38 g·kg-1·d-1 and 1.69 g·kg-1·d-1,every 8 hours for 2 days.Equal amounts of normal saline were administered to the normal control group and model group.At 6,24 and 48 hours after the molding,5 mL abdominal main artery blood from 5 rats were randomly collected from each group,and the blood was obtained by enzyme-linked immunosorbent assay(ELISA)to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),D-lactic acid,intestinal fatty acid-binding protein(I-FABP).At the same time,the ileum tissue was retained,and the protein expression of TLR4 and NF-κB in intestinal tissue was determined by Western blotting.Some of the ileal tissue was obtained for hematoxylin-eosin(HE)staining,and the intestinal histopathological changes were observed under light microscopy.Results The normal control group of rats had no significant change,and the other three groups showed heatstroke symptoms after mold making.The overall mortality in drug group were significantly lower than that in the model group[3.3%(1/30)vs.20.0%(3/15),P＜0.05].Compared with the normal control group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB in the model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group all increased.Compared with the model group,at 24 hours and 48 hours after molding in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB significant decreased[24 hours:TNF-α(ng/L):69.20±4.32,59.37±4.31 vs.76.99±5.02,IL-1(ng/L):132.68±4.93,112.59±9.64 vs.146.75±10.12,I-FABP(mmol/L):504.35±22.23,453.37±32.38 vs.542.58±13.83,D-lactic acid(mmol/L):114.55±8.52,90.57±3.09 vs.127.87±8.37,protein expression of TLR4(A value):1.50±0.08,1.23±0.01 vs.1.86±0.08,protein expression of NF-κB(A value):1.61±0.05,1.21±0.05 vs.1.97±0.08;48 hours:TNF-α(ng/L):58.46±5.13,38.98±5.53 vs.90.21±3.02,IL-1(ng/L):119.12±4.57,84.12±5.08 vs.170.20±6.21,I-FABP(mmol/L):436.04±27.63,321.85±22.03 vs.618.79±12.31,D-lactic acid(mmol/L):87.35±6.84,70.38±4.33 vs.154.14±10.83,protein expression of TLR4(A value):1.19±0.05,1.10±0.13 vs.2.09±0.06,protein expression of NF-κB(A value):1.15±0.09,0.97±0.08 vs.2.20±0.02,all P＜0.05].The expression levels of TNF-α,I-FABP,TLR4 and NF-κB protein in Dachaihu decoction high dose group decreased significantly at 24 hours and 48 hours compared with the standard dose group,however,IL-1 and D-lactic acid decreased significantly at 48 hours after molding(all P＜0.05).The pathology observation showed that,compared with the model group,the intestinal mucosa villus,the lamina propria drop and haemorrhage was decreased in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group.Telangiectasia was reduced and no ulcer formation was observed.Conclusion Dachaihu decoction can inhibit TLR4/NF-κB signaling pathway,reduce intestinal inflammatory response,thus reduce gastrointestinal damage,and protect the gastrointestinal mucosal barrier in rats with severe heatstroke.

Study on the value of diamine oxidase in the evalution of ulcerative colitis / 中国现代医生

Objective To investigate the value of peripheral blood diamine oxidase(DAO)in evaluating the severity of ulcerative colitis(UC).Methods A total of 76 UC patients admitted to Daxing Hospital,Capital Medical University from June 2020 to June 2022 were included in UC group,and were divided into severe ulcerative colitis(SUC)group and non-SUC group according to the severity of the disease.A total of 76 healthy subjects were included as control group.The general data and serum DAO of all subjects were collected for statistical analysis.Results The serum DAO level in UC group was significantly higher than that in control group(P<0.05).The serum DAO level in SUC group was significantly higher than that in non-SUC group(P<0.05).Receiver operating characteristic curve analysis showed that DAO predicted area under the curve(AUC)of UC was 0.751(95%CI:0.672-0.829,P<0.001),and DAO predicted AUC of SUC was 0.866(95%CI:0.807-0.925,P<0.001).Conclusion Serum DAO is an effective test index for evaluating the severity of UC,which is worthy of clinical promotion.

Role of the Sonic Hedgehog signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis / 临床肝胆病杂志

Objective To investigate the expression and role of the Sonic Hedgehog (Shh) signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 48 Sprague-Dawley rats were divided into sham-operation group (Sham group), SAP model group (SAP group), SAP+Shh signaling pathway-specific agonist purmorphamine group (PUR+SAP group), and SAP+Shh signaling pathway-specific antagonist cyclopamine group (CYC+SAP group) using a random number table, with 12 rats in each group, and each group was further divided into 12-hour and 24-hour subgroups, with 6 rats in each subgroup. Rats were given retrograde injection of 5% sodium taurocholate into the pancreatic and bile ducts to establish a model of SAP, and rats in the intervention groups were given intraperitoneal injection of 0.69 mg/kg purmorphamine and 0.69 mg/kg cyclopamine before modeling. Related samples were collected at 12 and 24 hours after modeling. HE staining was used to observe the pathological changes of the pancreas and the ileum; ELISA was used to measure the serum levels of amylase, lipase, diamine oxidase (DAO), and endotoxin-core antibody (EndoCAb); the TUNEL method was used to observe the apoptosis of intestinal epithelial cells; Western blot was used to measure the expression levels of Shh, Ptch1, and Gli1 in ileal tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results Compared with the Sham group, the SAP group had significant increases in the pathological scores of pancreatic and ileum tissue, the serum levels of lipase, amylase, DAO, and EndoCAb, the apoptosis of intestinal epithelial cells, and the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the PUR+SAP group had significantly alleviated pathological injury and dysfunction of the pancreas and intestine, a significant reduction in the apoptosis of intestinal epithelial cells, and significant increases in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the CYC+SAP group had significant aggravation of the pathological injury and dysfunction of the pancreas and intestine, a significant increase in the apoptosis of intestinal epithelial cells, and significant reductions in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Conclusion The Shh signaling pathway may be involved in intestinal mucosal barrier injury in SAP and exerts a protective effect.

Progress on the composition of intestinal mucosal barrier and its relationship with liver injury / 国际儿科学杂志

The complete mucosal barrier of the healthy intestine is the line of defense to prevent the translocation of substances.Many animal models and human pathological studies have proved that the changes of intestinal mucosal barrier function are closely related to the occurrence and treatment of liver disease.This review summarizes the composition of intestinal mucosal barrier, its interaction with liver injury and potential therapeutic targets.

Effect of heme oxygenase-1 modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion on intestinal barrier function in Brown Norway rats with acute rejection of liver transplantation / 中华肝胆外科杂志

Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) on the intestinal barrier function in rats with acute rejection of liver transplantation.Methods:Specific pathogen free 2 male Brown Norway (BN) rats (4-5 weeks, 40-60 g) were used to isolat BMMSCs, and HO-1 was infected by adenovirus. Of 24 male Lewis rats (7-8 weeks old, 200-220g) were used as donors, 30 male BN rats (8-9 weeks old, 220-240 g) were used as recipients. Acute rejection models of orthotopic liver transplantation were established in rats using two cuff technique. BN recipient rats were randomly divided into five groups: sham group, abdomen of the mice was open and closed within 30 min; NMP livers were simply mechanically perfused for 4 h; the BMP group were perfused with BMMSCs through the portal vein; the HBP group were perfused with HO-1/BMMSCs through the portal vein; the FK506 livers were mechanically perfused for 4 h and administered intragastrically of tacrolimus daily following surgery, 6 per group, on days 14 after surgery, the relevant indicators were taken and the rejection activity index (RAI) changes were investigated. The changes of intestinal pathological were analyzed by HE staining and transmission electron microscope, the expression levels of zonula occludens-1 (ZO-1) and occludin protein in intestinal tissue were detected by Western blotting, the concentrations of lipopolysaccharide, D-lactic acid and diamine oxidase (DAO) in serum were detected by ELISA.Results:The RAI of HBP group (2.80±0.84) and FK506 group (2.20±0.84) were significantly lower than that of NMP group (7.60±1.14) and BMP group (6.00±1.58), the differences were statistically significant (all P<0.05). The intestinal villi in NMP group were significantly sparse, wrinkled and disorderly arranged while the degree of intestinal injury in BMP group, HBP group and FK506 group were more mitigated. Electron microscope observation showed that the microvilli of intestinal epithelial cells in HBP group were rich and orderly, and the tight junction structure between cells was complete. The protein expression levels of ZO-1 and Occludin in the intestinal tissues of HBP group [(0.87±0.06) (1.28±0.26)] were higher than those of NMP group [(0.41±0.12) (0.27±0.18)] and FK506 group [(0.52±0.15) (0.63±0.22)], the differences were statistically significant (all P<0.05). The concentration of lipopolysaccharide, D-lactic acid and DAO in serum of HBP group was lower than those of NMP group and FK506 group, the differences were statistically significant (all P<0.05). Conclusion:HO-1/BMMSCs combined with NMP protects the intestinal mucosal barrier function of BN rats with acute rejection after liver transplantation.

Study on the effects of Qingjie huagong decoction on the regulation of intestinal flora and intestinal mucosal barrier in severe acute pancreatitis model rats / 中国药房

OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis （SAP）mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ，interleukin 10（IL-10），IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin，ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ，abdominal distension symptoms of SAP model rats were significantly relieved ，and their mental state recovered better ；the levels of serum amylase and IL- 18 in serum were decreased significantly （P＜0.05），while the level of IL- 10 was increased significantly （P＜0.05）. The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced ， the degree of intestinal epithelial cell structural disorder was alleviated ，and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly （P＜0.05），and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ，reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.

Effects of compound fermented milk on improving constipation in mice and underlying mechanism / 中华微生物学和免疫学杂志

Objective:To investigate the effects of compound fermented milk on intestinal microbiota, short chain fatty acid (SCFA), intestinal motility and mucosal barrier in mice with constipation.Methods:Twenty-seven C57BL/6JNifdc mice were randomly divided into three groups: control group, model group and intervention group. The model group and the intervention group were given loperamide intragastrically for two weeks. Starting from the second week, the intervention group was treated with compound fermented milk for 7 d. The control group was given normal saline. Food intake, water intake, weight change, fecal moisture content, time of first-time black stool and small intestine propulsion rate were detected. Expression of serotonin C receptor (5-HTR2C), zona occludins-1 (ZO-1) and mucin-2 (MUC-2) at mRNA level in colon was analyzed. Western blot was used to measure the expression of Raf/ERK/MAPK-related proteins. SCFA level in intestinal tract was detected by gas chromatography. Intestinal microbiota diversity was analyzed by high-throughput sequencing.Results:Compared with the control group, the first black stool excretion time was significantly prolonged in the model group ( P<0.01). Moreover, fecal moisture content, small intestine propulsion rate and the expression of 5-HTR2C and ZO-1 at mRNA level in colon were significantly decreased ( P<0.01). Compared with the model group, the first black stool excretion time was significantly shortened ( P<0.05); fecal moisture content, small intestine propelling rate ( P<0.05), the expression of colon 5-HTR2C and ZO-1 at mRNA level ( P<0.05), phosphorylation of Raf/ERK/MAPK pathway in the colon, intestinal SCFA-producing bacteria and intestinal SCFA content were increased in the intervention group. Conclusions:Compound fermented milk had a therapeutic effect on constipation in a mouse model by increasing the abundance of SCFA-producing bacteria and SCFA content, enhancing the phosphorylation of the Raf/ERK/MAPK pathway to up-regulate the expression of 5-HTR2C at mRNA level in the colon, and increasing the expression of ZO-1 at mRNA level in the colon. Intestinal peristalsis and intestinal mucosal barrier function were enhanced, thus improving the symptom of constipation.

Effects of different doses of dexmedetomidine on levels of serum claudin-1 and diamine oxidase in patients undergoing laparoscopic radical resection of gynecological malignant tumors / 肿瘤研究与临床

Objective:To explore the effect of different doses of dexmedetomidine (Dex) on levels of tight-junction protein claudin-1 and diamine oxidase (DAO) in patients undergoing laparoscopic radical resection of gynecological malignant tumors.Methods:A total of 60 patients with gynecological malignant tumors who were scheduled to undergo laparoscopic radical resection under general anesthesia from January 2019 to January 2020 in the Second Hospital of Shanxi Medical University were selected, including 43 cases of cervical cancer (stageⅠ-Ⅱ A), 9 cases of ovarian cancer (stageⅠ A-Ⅲ C), and 8 cases of endometrial carcinoma (stageⅠ). Accroding to the random number table method, the patients were divided into control group (group C), low-dose Dex group (group D 1) and high-dose Dex group (group D 2), with 20 cases in each group. Patients in group D 1 were given Dex 0.5 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Patients in group D 2 were given Dex 1.0 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Group C adopted the same calculation method and received the same amount of 0.9% sodium chloride solution by infusion pump. At 10 min before induction (T 1), 1 hour after pneumoperitoneum (T 2) and 12 hours after pneumoperitoneum (T 3), 5 ml of brachial vein blood was collected from the patients, and the levels of claudin-1 protein, DAO and blood glucose were measured. Results:At T 1, T 2 and T 3, the expression levels of claudin-1 in group C were (77.05±17.61) pg/ml, (66.76±12.97) pg/ml and (55.93±12.71) pg/ml, and the difference was statistically significant ( F = 10.449, P<0.05); the expression levels of DAO in group C were (4.83±0.93) ng/ml, (5.62±1.01) ng/ml and (5.98±1.21) ng/ml, and the difference was statistically significant ( F = 6.139, P < 0.05); the levels of blood glucose in group C were (4.82±0.66) mmol/L, (7.55±0.94) mmol/L and (6.51±0.54) mmol/L, and the difference was statistically significant ( F = 70.197, P < 0.05). At T 2, the expression level of claudin-1 in group D 1 was (69.12±13.02) pg/ml, which was not significantly different from group C ( t = -0.575, P > 0.05); the expression level of claudin-1 in group D 2 was (76.36±14.89) pg/ml, which was higher than that in group C, and the difference was statistically significant ( t = -2.175, P < 0.05). At T 3, the expression levels of claudin-1 in group D 1 and group D 2 were (66.14±14.36) pg/ml and (73.37±16.93) pg/ml, which were higher than that in group C, and the differences were statistically significant ( t values were -2.380 and -3.682, both P < 0.05). The expression levels of DAO in group D 1 and group D 2 were (5.02±0.84) ng/ml and (4.91±0.93) ng/ml at T 2, and (5.29±0.86) ng/ml and (5.20±0.98) ng/ml at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.051, 2.295, 2.079 and 2.285, all P < 0.05). The levels of blood glucose in group D 1 and group D 2 were (7.10±0.66) mmol/L and (6.77±0.97) mmol/L at T 2, and (5.95±0.94) mmol/L and (5.93±0.74) mmol/L at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.565, 5.374, 2.293 and 2.765, all P < 0.05). Conclusion:Continuous infusion of Dex can inhibit the stress response caused by long-term CO 2 pneumoperitoneum in laparoscopic radical resection of gynecological malignant tumors, and adjust the changes of expression levels of claudin-1 protein and DAO, reduce the damage of intestinal mucosal cells, facilitate the recovery of intestinal function, and the effect of high-dose Dex is better than low-dose Dex.