Endoplasmic reticulum stress and NOD-like receptor protein 3 involves in intestinal mucosal injury induced by severe heat stroke / 中华急诊医学杂志

Objective:To observe whether endoplasmic reticulum stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation were involved in severe heat stroke induced intestinal mucosal injury and to investigate the potential protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA).Methods:Thirty male BALB/c mice were randomly (random number) assigned to 3 groups: the control group, heat stroke group (HS), and 4-PBA pretreatment group (4-PBA+HS, 4-PBA 120 mg/kg, intraperitoneal injection). Mice in the control group were placed at room temperature, while mice in the HS group and 4-PBA+HS group were placed in a prewarmed chamber [temperature (35.5±0.5) °C, humidity (60.0±5.0)%]. A rectal temperature (Tc) that reached 42 °C was considered to indicate severe heat stroke. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) in intestinal homogenate were analyzed by a colorimetric method, serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) were assessed by ELISA, intestinal histopathology was evaluated by hematoxylin and eosin (HE) staining, intestinal ultrastructure was observed by electron microscopy, and the protein expression of GRP78, CHOP, NLRP3 and cleaved caspase-1 were analyzed by Western blot. Data were statistically analyzed by ANOVA test and LSD- t multiple comparison test if homogeneous variance, or analyzed by Welch test and Dunnett's T3 multiple comparison test if heterogeneous variance. Results:The concentration of MDA in the HS group was increased ( t=14.243, P<0.01), while SOD was decreased compared with that in the control group ( t=7.781, P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly elevated ( t=12.664, P<0.01; t=16.240, P<0.01). Under light microscopy, extensive destruction of small intestinal villi and inflammatory cell infiltration were observed in the intestines of mice with severe heat stroke. Transmission electron microscopy showed that endoplasmic reticulum structures were significantly expanded, and mitochondria were vacuolated in the intestines of mice with severe heat stroke. Compared with those in the control group, the protein expression levels of GRP78, CHOP, NLRP3 and cleaved caspase-1 in the small intestine were elevated in the HS group ( t=14.824, P <0.01; t=12.667, P<0.01; t=9.298, P<0.01; and t=6.588, P=0.001). Compared with those in the HS group, mice in the 4-PBA pretreatment group exhibited reduced concentrations of MDA ( t=9.167, P<0.01), increased SOD ( t=6.077, P<0.01) , and reduced serum IL-1β and IL-18 levels ( t=4.889, P= 0.001; t=5.693, P<0.01). In addition, 4-PBA pretreatment significantly alleviated the pathological disruption and ultrastructural damage to small intestine tissues. Moreover, 4-PBA pretreatment reduced GRP78, CHOP , NLRP3 and cleaved caspase-1 protein expression ( t=9.080, P<0.01; t=7.152, P<0.01; t=4.249, P=0.005; t=3.650, P=0.011). Conclusions:Endoplasmic reticulum stress and NLRP3 inflammasome are involved in intestinal mucosal injury induced by severe heat stroke. 4-PBA plays a protective role by alleviating endoplasmic reticulum stress and NLRP3 inflammasome activation.

Effect of Weikang Capsule () on Aspirin-Related Gastric and Small Intestinal Mucosal Injury / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Weikang Capsule (, WKC) on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy (MCCE).@*METHODS@#Patients taking enteric-coated aspirin aged 40-75 years were enrolled in Beijing Anzhen Hospital, Capital Medical University from January 2019 to December 2019. The patients continued taking aspirin Tablet (100 mg per day) and underwent MCCE before and after 1-month combined treatment with WKC (0.9 g per time orally, 3 times per day). The gastrointestinal symptom score, gastric Lanza score, the duodenal, jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment. Adverse events including nausea, vomiting, abdominal pain, abdominal distension, abdominal discomfort, dizziness, or headache during MCCE and combined treatment were observed and recorded.@*RESULTS@#Twenty-two patients (male/female, 13/9) taking enteric-coated aspirin aged 59.5 ± 11.3 years with a duration of aspirin use of 28.0 (1.0, 48.0) months were recruited. Compared with pre-treatment, the gastrointestinal symptom rating scale scores, gastric Lanza scores, and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment (P<0.05), and jejunal and ileal mucosal injury scores showed no obvious change. No adverse events occurred during the trial.@*CONCLUSIONS@#WKC can alleviate gastrointestinal symptoms, as well as gastric and duodenal mucosal injuries, in patients taking enteric-coated aspirin; it does not aggravate jejunal or ileal mucosal injury, which may be an effective alternative for these patients (Clinical trial registry No. ChiCTR1900025451).

Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Protective effects of Dendrobium officinale superfine powder against LPS-induced intestinal mucosal injury in mice / 中国中药杂志

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.

Multivariate statistical analysis of Evans blue exudation spots and acupoint sensitization distribution in rats with acute intestinal mucosal injury / 针刺研究

OBJECTIVE: To observe the distribution characters of Evans Blue (EB) exudation spots in the abdominal area in acute intestinal mucosal injury (AIMI) rats by using latitude and longitude grid counting and multivariate statistical analysis and to explore the feasibility of these methods. METHODS: Twenty-four SD rats were randomly divided into blank control, 7.5%, 10%, and 12.5% mustard oil groups (n＝6 rats in each group). The AIMI model was established by mustard oil enema, followed by injection of EB (0.1 mL/100g) into the tail vein. At 5, 10, 15, 20 and 25 h after EB injection, the rats under anesthesia were fixed in supine position for observing and photographing the abdominal subcutaneous EB exudation spots. The H．E. staining was used to observe histopathological changes of colonic mucosa. The longitude and latitude grids of the abdominal region were constructed (by taking the midpoint of the superior sternum as the origin) to determine the position of the blue spots. That the coordinate grids of the two regions can be connected geometrically is termed as "characteristic region". The data were processed by using multivariate statistical analysis. RESULTS: ① H．E. staining showed edema and inflammatory cell infiltration after colonic enema of different concentrations of mustard oil. ② Clustering analysis indicated that the distribution of exudation points in the "characteristic grid" had no temporal variation trend, and was not related with the concentration of mustard oil (P>0.05). ③ Factor analysis and contour analysis about the exudation spots of EB at 7.5% concentration showed that the "characteristic region Ⅱ" of different factors presented a tendency of time-dependent exudation, i．e. reduction of exudation degree along with time (P<0.05), and it is located near "Tianshu" acupoint. ④At 5 h after injection of EB, the 8 "characteristic regions" presented an EB-concentration-dependent tendency (reduction in exudation degree along with the increase of EB-concentration), among which the exudation degree of region C (near "Tianshu" acupoint) of the abdomen was higher (P<0.05). CONCLUSION: The multivariate statistical analysis method can be used to identify the abdominal "characteristic regions" of exudation spots of EB in rats with AIMI, and the characteristic region has acupoint sensitization characteristics related to the time and severity of mucosal injury.

Study on Repair Effect of Artificial Isaria cicadae on Intestinal Mucosal Injury Induced by 5-Fluorouracil in Rats / 中国药房

OBJECTIVE： To study the repair effect of artificial Isaria cicadae on intestinal mucosal injury induced by 5-fluorouracil （5-FU） in rats. METHODS： Forty SD rats were randomly divided into normal group （normal saline）， model group （normal saline）， artificial I. cicadae high-dose， medium-dose and low-dose groups （3.5， 1.75， 0.875 g/kg）， with 8 rats in each group. Except for normal group， other groups were given intraperitoneal injection of 5-FU （0.25 g/10 mL） 30 mg/kg， once a day， for consecutive 5 days. At the same time， each group was given relevant medicine/normal saline intragastrically， once a day， for consecutive 8 d. After medication， body weight of rat was determined in each group. HE staining was used to observe the pathological change of small intestine. The levels of biobarrier-related factor [endotoxin （ET）， D-lactic acid （D-LA）]， immune barrier related factors （TNF-α， IFN-γ， sIgA， IL-15， G-CSF in serum and MPO， MDA in small intestine） and the levels of mechanical barrier related factors （connexin ZO-1 and Claudin-1） were detected. RESULTS： Compared with normal group， body weight of rats in model group was decreased significantly （P＜0.01）. Intestinal villus exfoliated obviously， the crypt structure was scattered， a large number of inflammatory cells gathered， and intestinal mucosa was seriously damaged. Serum levels of ET and D-LA， the levels of TNF-a， IFN-γ， MPO and G-CSF in serum， MDA level in small intestine were increased significantly （P＜0.01）. Serum levels of sIgA and IL-15 as well as the expressions of ZO-1 and Claudin-1 in small intestine were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， body weight of rats in artificial I. cicadae high-dose group was increased significantly （P＜0.01）. The pathological changes of the small intestine of rats in each administration group were improved to varying degrees. The intestine morphology of artificial I. cicadae high-dose and medium-dose groups was close to that of the normal group. The levels of and ET， D-LA， TNF-α， IFN-γ， MPO， G-CSF in serum and the level of MDA in intestinal were decreased significantly （P＜0.01）. Serum levels of   sIgA and IL-15 in administration groups as well as the expressions of ZO-1 and Claudin-1 in intestinal tissue were increased significantly （P＜0.01）. CONCLUSIONS： Artificial I. cicadae can repair intestinal mucosal damage caused by 5-FU in respects of mechanical barrier， immune barrier， biological barrier.

Influence of different CO2 pneumoperitoneum pressure on intestinal mucosal injury and intestinal function recovery in patients undergoing laparoscopic radical gastrectomy / 中国现代普通外科进展

Objective:To evaluate the influence of different CO2 pneumoperitoneum pressure on intestinal mucosal injury and intestinal function recovery in patients undergoing laparoscopic radical gastrectomy.Methods:A total of 120 patients undergoing laparoscopic radical gastrectomy were randomly divided into group A,B and C.Each group included 40 patients.CO2 pneumoperitoneum pressure ingroup A,B and C were 8～10 mmHg,11～13 mmHg and 14～16 mmHg,respectively.The degree of intestinal mucosa damage,plasma D-lactate(2,24 and 48 hours after the treat-ment),intestinal function recovery and complication ration were compared between the three groups.Results:Damage degree of intestinal mucosa after operation in A,B and C groups were 0～1,1～2 and 2～3 respectively.There was significant change in intestinal mucosa injury after operation in both B and C groups.The level of D-lactic acid in group C (2,24 and 48 hours after the treat-ment) were significantly higher those in group A and group B (P＜0.05).The bowel sounds appeared time,exhaust time and intake time in group C were significantly longer than group A and group B (P＜0.05).The incidence of complications were not significantly difference during the three groups.Conclusion:The high pressure of CO2 pneumoperitoneum will cause intestinal mucosa damaged,and not conducive to the patients' intestinal rehabilitation.We suggest that the CO2 pneumoperitoneum pressure should be as low as possible under clear visualization during operation.

Characterization of taste-masking dry emulsion of azithromycin by in vitro and in vivo evaluation / 药学学报

To develop a taste-masking oral preparation of azithromycin for pediatrics, the reversed lipid nano-micelle techniques were used to mask the bitterness of azithromycin. Dry emulsion (DE) for taste-masking was prepared by solidifying the reversed-micelle oil solution containing azithromycin. Colloidal silicon dioxide was used as absorbent and solid carrier. Solidification was confirmed through dying test and observed by scanning electron microscope (SEM). The DE formulation was characterized by X-ray powder diffraction and SEM in order to investigate the crystal state of drug. Reconstitution emulsion droplet size and morphology were also determined using Nano ZS90 Zetasizer and transmission electron microscopy (TEM). The taste testing was performed in two different ways, namely, human taste panel test and the measurement of the amount of drug released in simulated oral cavity condition. The intestinal mucosal irritation test of DE formulation was also investigated in rats in comparison with commercial product (Zithromax). The optimal taste-masking formulation of azithromycin can be re-dispersed immediately with mean diameter of 530.1 nm after agitation in water. The results of taste testing showed that the bitterness of azithromycin was successfully masked by DE formulation similar with Zithromax at the same dose, moreover reduced intestinal irritation compared to Zithromax. These results indicate that the DE formulation for taste-masking of azithromycin is promising and valuable in the future development of azithromycin for pediatrics.

Protective Effect of ω-6 Soybean Oil Fat Emulsion on Folium Sennae-induced Diarrhea in Mice / 中国医科大学学报

Objective To investigate the protective effect of ω?6 soybean oil fat emulsion on folium sennae?induced diarrhea in mice. Methods Thirty?six Kunming mice were randomly divided into three groups,including control,diarrhea,ω?6 soybean oil fat emulsion group(12 mice in each group). Besides the mice in control group,other mice were administrated folium sennae by gavage for 15 days to establish the diarrhea model. Then mice in ω?6 soybean oil fat emulsion group received ω?6 soybean oil fat emulsion by intravenously administration at a dose of 15 mL/kg daily since 6th day after intragastric administration of folium sennae for 10 days. Animals in control group and diarrhea group were intravenously adminis?tered with same volume of saline. The body weight ,general state and diarrhea index of the mice in each group were dynamically assessed. Ten days after intravenous injection,mice in every group were sacrificed and tissues were collected. Morphology of intestine mucosa was observed after HE staining. Albumin(ALB)level in plasma was evaluated by biochemical method. Proliferating cell nuclear antigen(PCNA)expression in intestine mucosa were assessed by immunohistochemical method. Results Compared with that in the diarrhea group,the general status,body weight and diarrhea index of mice in ω?6 soybean oil fat emulsion group were improved significantly. Ten days after intravenously administration ,pathological change in intestine mucosa of mice in ω?6 soybean oil fat emulsion group was improved significantly ,ALB level in plasma and PCNA expression in intestine mucosa were significantly increased(P<0.05)compared with that in diarrhea group. Conclusion ω?6 soybean oil fat emulsion has a significant protective effect on the diarrhea of mice induced by folium sennae ,which may be related to the up?regulated expression of PCNA by ω?6 soybean oil fat emulsion.

Treatment of radiation-induced intestinal mucosal injury with keratinocyte growth factor 2 mutant in mice / 军事医学

Objective To investigate the therapeutic effect of KGF-2 mutants on radiation-induced intestinal mucosal injury.Methods Specific pathogen free (SPF) female C57BL/6J mice were randomly divided into 4 groups, which were treated with/without KGF2 mutant and/or bone marrow cell transplantation.All the 4 groups were radiated with one-time whole bodyγ-ray exposure of 12 Gy.Also one untreated group was included as control.The therapeutic effect of recombi-nant human KGF-2 mutants on radiation-induced intestinal mucosal injury was analyzed by the survival rate at the 30th day, the pathological change and the apoptosis as well as autophagy status of small intestine at 72 hours after exposure.Results After irradiation, all the mice in the untreated group died within 9 days while the mice treated with KGF-2 mutant combined with bone marrow cell transplantation showed a 70%survival rate at the 30th day.We also found that intestinal mucosa of the mice in this group had a more intact structure, a higher level of autophagy and a lower level of apoptosis via HE staining and immunohistochemistry.Conclusion KGF-2 mutant has a significant therapeutic effect on radiation-induced intestinal mucosal injury.

Establishment and assessment of a rat model of persistent intestinal mucosal injury induced by methotrexate / 中国实验动物学报

Objective To establish a rat model of persistent intestinal mucosal injury.Methods The rat model of persistent intestinal mucosal injury was induced by intraperitoneal injection of methotrexate.The food intake and body weight of all the rats were recorded.Pathological changes were observed using HE staining, the level of D-lactate and diam-ine oxidase in plasma, and myeloperoxidase and malondiadehyde in the intestinal tissue were measured by biochemistry. Results After modeling, the rat body weight and food intake were decreased.On day 4, the scores of mucosal damage, the levels of plasma D-lactate, DAO, MPO and MDA were significantly increased (P<0.05).On day 5, the intestinal damages of rats began to restore, and there was no significant difference among groups on day 6.The symptoms after the secondary injection were similar to those after the first injection, and the rats recovered gradually at day 12.Conclusions Intestinal mucosal injury in rats induced by 20 mg/kg MTX is an acute injury process, the course only lasts for 4-5 days. Intermittent injections twice of 10 mg/kg MTX can cause persistent intestinal mucosal injury in rats.This persistent injury model is more suitable for nutritional therapy evaluation in medium-and long-term studies of nutritional therapy.

Impact of intestinal ischemia/reperfusion on free amino acid levels in plasma / 中华临床营养杂志

Objective To investigate intestinal mucosal injury and the change of free amino acid levels in plasma with intestinal ischemia/reperfusion.Methods Twenty-four Sprague-Dawley (SD) male rats (SPF grade) were randomly divided into 3 groups with 8 rats in each group:Blank group,Sham group and ischemia/reperfusion (I/R) group.The rats in I/R group were subjected to 60 min ischemia by clamping the superior mesenteric artery (SMA),followed by 120 min repeffusion.All rats were sacrificed with blood withdraw through inferior vena cava.The plasma was precipitated with Sulfosalicylic acid and the supernatant free amino acid levels were measured and the intestinal mucosal thickness and villus length were also assayed.Results In the I/R group the total free amino acids,essential amino acids (EAA),glutamine and branched-chain amino acids (BCCA) were remarkably lower [the total free amino acids:I/R vs Blank vs Sham:(4585.1 326.1) vs (5661.5 ±581.9) vs (5337.9±998.7) μmol/L (F=5.075,P=0.016); EAA:I/Rvs Blank vs Sham:(1401.3 ±183.4) vs (2147.6 ± 265.1) vs (1796.2 ± 440.8) μmol/L (F =1 1.216,P =0.000) ; glutamine:I/R vs Blank vs Sham:(646.1 ± 34.7) vs (895.7 ± 258.8) vs (839.1 ± 163.7) μmol/L (F =4.326,P =0.027) ; BCCA:I/R vs Blank vs Sham:(507.8 ± 119.0) vs (912.2 ± 165.8) vs (671.9 ± 79.8) μmol/L (F =10.662,P =0.001)]and the jejunum and ileum mucosal thickness and villus height were decreased compared to Blank and Sham groups [jejunum mucosal thickness:I/R vs Blank vs Sham:(401.50 ± 117.79) vs (529.22 ±54.73) vs (499.54 ±64.48) μm (F=31.869,P =0.000) ; jejunum villus height:I/R vs Blank vs Sham:(271.37 ± 84.29) vs (365.26 ± 46.98) vs (349.67 ± 56.11) μm (F =30.472,P =0.000) ; ileum mucosal thickness:I/R vs Blank vs Sham:(254.20 ± 43.56) vs (324.70 ± 30.56) vs (298.26 ± 58.46) μm (F =30.442,P =0.000) ; ileum villus height:I/R vs Blank vs Sham:(169.37 ± 37.25) vs (221.62 ± 37.26) vs (193.25 ± 38.39) μm (F =24.145,P =0.000)],and The EAA and BCAA in the I/R group were lower than the Sham group (respectively,P ＜0.05).There was no significant difference in aromatic amino acids (AAA) among the three groups [I/R vs Blank vs Sham:(273.2 ± 37.4) vs (296.8 ± 55.6) vs (281.9 ± 7.3) μmol/L (F =0.578,P =0.570)].The ratio BCAA/AAA in the Sham and I/R groups were significantly lower than the Blank group [(I/R vs Blank vs Sham:(2.4 ±0.6) vs.(1.9 ±0.4) vs (3.1 ±0.7) (F =5.215,P =0.014)],while the I/R group was decreased slightly compared to the Sham group,but the difference was not significant (P ＞ 0.05).The ethanolamine phosphate,taurine,citrulline,cystine,phosphoserine levels were reduced in the Sham and I/R groups compared to the Blank group [ethanolamine phosphate:I/R vs Blank vs Sham:(11.4 ± 1.9) vs (14.3 ± 3.4) vs (10.1±1.7) μmol/L(F=5.897,P=0.009);taurine:I/R vs BlankvsSham:(341.1±36.3) vs(533.2±90.8) vs (439.2±105.4) μmol/L (F=10.702,P=0.001); citrulline:I/R vs Blank vs Sham:(57.7±3.2) vs (73.1 ±16.2) vs (58.1 ±3.8) μmol/L (F=6.360,P =0.007); cystine:I/R vs Blank vs Sham:(20.0 ± 3.6) vs (60.6 ± 24.6) vs (36.3 ± 5.8) μmol/L (F =15.344,P =0.000) ; phosphoserine:I/R vs BlankvsSham:(10.2±1.1) vs (15.8±5.4) vs (11.7 ±3.4) μmol/L (F=4.878,P=0.018)],and the taurine and cystine in I/R groups were significantly decreased than the Sham group (respectively,P ＜ 0.05).The ornithine and arginine were comparatively reduced in I/R in contrast to the Blank and Sham groups [ornithine:I/R vs Blank vs Sham:(81.5 ± 19.0) vs (125.5 ±42.3) vs (114.9 ± 19.5) μmol/L (F =4.961,P =0.017) ;arginine:I/R vs Blank vs Sham:(199.2 ± 8.0) vs (258.9 ± 14.6) vs (248.7 ± 38.4) μmol/L (F =13.940,P =0.000)].The tryptophan and glutamic acid concentrations were increased in the Sham and I/R groups [tryptophan:L/R vs Blank vs Sham:(125.9 ± 12.1) vs (103.1 ± 29.9) vs (128.9 ± 18.5) μmol/L (F =5.429,P =0.031) ; glutamic acid:I/R vs Blank vs Sham:(188.6 ± 29.8) vs (93.6 ± 29.4) vs (125.4 ± 43.8) μmol/L (F =15.241,P =0.000)] and it was lower in the Sham group than the I/R group (P ＜ 0.05).Conclusion Intestinal ischemia-reperfusion can cause intestinal mucosal injury and the change of free amino acid levels in plasma and intestinal barrier damage may be related to the decline glutamine concentration and the increase of protein catabolism.

Values of histidine decarboxylase,intestinal fatty acid binding protein,and diamine oxidase for diagnosing intestinal mucosal injury in patients with intestinal obstruction / 中华临床营养杂志

Objective To investigate the clinical values of serum histidine decarboxylase(HDC),intestinal fatty acid binding protein(I-FABP),and diamine oxidase(DAO)for diagnosing intestinal mucosal injury (IMI)in patients with intestinal obstruction.Methods The expression levels of serum HDC,I-FABP,and DAO in 28 patients with strangulated intestinal obstruction,19 patients with simple intestinal obstruction,17 patients with acute simple appendicitis,and 20 healthy control were determined by enzyme-linked immunosorbent assay (ELISA)before clinical treatment,and then the areaa under receiver operating characteristic curves(AUC)of these diagnostic indicators were compared.In addition,the incidences of systemic inflammatory response syndrome (SIRS)and infectious complications were closely observed.The difference of the expressions of HDC,I-FABP,and DAO and their relationship with SIRS and infectious complications were compared among these patients and controls.Results The expression levels of serum HDC, I-FABP, and DAO were the highest in patients with strangulated intestinal obstruction (all P < 0.001), and the expression levels of these three indicators were significantly higher in patients with simple intestinal obstruction than in those with acute simple appendicitis or healthy controls (all P<0.05).The AUC of HDC (0.913) was significantly larger than that of I-FABP (0.877, P =0.000) and DAO (0.873, P = 0.000).When the cut-off value of HDC ≥31.00 ng/ml, the sensitivity, specificity, false negative rate, and false positive rate of HDC were 74.5% , 94.6% , 25.5% , and 5.4% , respectively,which were all better than those of I-FABP and DAO.There were significant differences of the incidence of SIRS ( P = 0.046) and abdominal infection (P = 0.027) among patients with strangulated intestinal obstruction, patients with simple intestinal obstruction, and patients with acute simple appendicitis, while lung infection showed no such significant difference (P = 0.728).The expression level of serum HDC was significantly higher in patients with strangulated intestinal obstruction who were also suffered from SIRS ( P = 0.000) or abdominal infection ( P =0.002) than that of uninfected patients.Meanwhile, the expression levels of serum I-FABP and DAO were significantly higher in the SIRS patients with strangulated intestinal obstruction than that of uninfected patients ( P = 0.027, P=0.017, respectively).The expression levels of HDC, I-FABP, and DAO were significantly correlated with the incideces of SIRS and abdominal infection ( all P < 0.05 ) , among which the level of HDC and the incidence of SIRS had the highest correlation (R = 0.608, P = 0.001).Conclusion HDC can be an effective indicator for diagnosing IMI in patients with intestinal obstruction.