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Intestinal barrier dysfunction refers to the damage or even atrophy of the intestinal mucosa,disorder of intestinal microbial population and increased intestinal permeability caused by a variety of factors,resulting in the insertion of bacterial and/or endotoxin translocation into other tissues and/or blood circulation,induction and/or aggravation systemic multiple organ dysfunction and inflammatory response.The destruction of the intestinal barrier is associated with many gastrointestinal disorders,bur also accompanied by parenteral pathological conditions,such as allergic diseases.Therefore,maintaining a healthy intestinal barrier is critical to children.At present,there are relatively few studies on the intestinal barrier dysfunction in children.This paper reviews the recent progress in the pathogenesis of intestinal barrier in children.
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Objective To investigate the effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction of human intestinal epithelial (Caco2) cells. Methods Caco2 cells (passages 28-35) were purchased from the Cell Bank of the Shanghai Institute of Cell Biology, Chinese Academy of Sciences in Shanghai, China, and they were cultured in Dulbecco minimum essential medium (DMEM) containing 20% fetal bovine serum. These cells were randomly divided into four groups: control group (group A), hydrogen-rich medium group (group B), LPS group (group C) and LPS + hydrogen-rich medium group (group D). Cells were cultured with normal medium in group A and group C or with hydrogen-rich medium in group B and group D. Meanwhile, 1 g/L LPS was simultaneously added into group C and group D, while an equivalent volume of normal saline was added into group A and group B instead. In vitro intestinal epithelial models were reproduced with monolayer filter-grown Caco2 and intestinal epithelium. The trans-epithelial electrical resistance (TEER) in models of each group was measured at different incubation times (0, 3, 6, 12, 24 and 48 hours). Cell viability and cytotoxicity were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release assay, respectively, after incubation for 24 hours. The expression levels of claudin-1 and occludin were respectively determined at 6, 12 and 24 hours of incubation by Western Blot assay. The morphological structure of claudin-1 and occludin was respectively observed after incubation for 24 hours with immunofluorescence staining. Results There was no statistical significance in variables between group A and group B. Compared with group A, it was shown that TEER was time-dependently decreased in groups C and D after 6 hours. Compared with group C, TEER in group D was increased after 6 hours. Compared with group A, the cell viability was significantly reduced in group C [(67.2±7.9)% vs. (100.0±0.0)%, P < 0.05] and cell injury was obvious [LDH release rate: (38.5±2.1)% vs. (1.2±0.3)%, P < 0.05]; the expression levels of claudin-1 and occludin at 6, 12, 24 hours were significantly down-regulated [claudin-1 (gray value): 0.351±0.079, 0.272±0.075, 0.190±0.049 vs. 0.518±0.030; occludin (gray value): 0.416±0.044, 0.290±0.062, 0.226±0.019 vs. 0.602±0.038, all P < 0.05], and the structure of claudin-1 and occludin were profoundly disrupted. Compared with group C, it was shown that the cell viability was significantly increased in group D [(88.8±7.4)% vs. (67.2±7.9)%, P < 0.05] and cell injury was significantly abated [LDH release rate: (16.4±4.3)% vs. (38.5±2.1)%, P < 0.05]; the expression levels of claudin-1 and occludin were significantly up-regulated at 24 hours [claudin-1 (gray value): 0.428±0.046 vs. 0.190±0.049, occludin (gray value): 0.466±0.071 vs. 0.226±0.019, both P < 0.05]; the disrupted structures of claudin-1 and occludin were partially recovered. Conclusion Hydrogen-rich medium can effectively attenuate LPS-induced dysfunction of intestinal epithelial barrier in human Caco2 cells by ameliorating cell viability as well as regulating claudin-1 and occludin expression and structure.
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Necrotizing enterocolitis ( NEC) is one of the most serious diseases of digestive system dur-ing neonatal period,which is one of the main cause of premature death. The components which maintain the in-testinal barrier function of newborns,especially the premature infants,are always underdeveloped,and easily to be damaged. Thus,the formation of tight junctions between epithelial cells is broken,the early intestinal peristal-sis established delayed,and the secretion of sIgA is reduced. These pathogenic factors induce serious complica-tions,such as intestinal barrier dysfunction,bacterial translocation and sepsis. Hypoxia ischemia,inflammation, infection can either cause intestinal mechanical barrier damage. The delay of micro ecological barrier establish-ment,the immature of immune barriers,intestinal microcirculation dysfunction are all involved in the occurrence of NEC. In addition,miRNA also plays an important role in the regulation of intestinal epithelial cell differentia-tion,structure and barrier function. Pathological changes of NEC are the result of intestinal barrier dysfunction, and the injury of intestinal barrier function will aggravate NEC pathological changes. Therefore, understanding the role of intestinal barrier dysfunction in the pathogenesis of NEC may improve the prevention and treatment of NEC.
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Objective To observe the protection of carbachol on intestinal barrier function in patients with trauma. Methods A prospective randomized controlled trial was conducted. Seventy patients after trauma with a definite diagnosis of multiple organ dysfunction syndrome(MODS)from Department of Critical Care Medicine in Hebei United University Affiliated Hospital were included. According to random number table,the patients were divided into a carbachol treatment group(37 cases)and a mosapride citrate treatment group(33 cases),and all the patients in the two groups were treated by antibacterial drugs,supportive agents for organ function,surgery, etc symptomatic treatment. Based on the conventional treatment,in the carbachol treatment group,carbachol was administered through a stomach tube at the dose of 0.2 mg/kg,twice a day,and the dose was doubled if no exhaust or defecation persisted for 3 days after treatment,while in the mosapride group,mosapride citrate was given at the dose of 5 mg once and thrice a day,the therapeutic course of both groups being 7 days. On the 1st,3rd,5th, 7th day after admission,peripheral venous fasting blood in early morning was collected,the activity of diamine oxidase(DAO),expression rates of CD11b+and CD18+in polymorphonuclear neutrophil(PMN),contents of tumour necrosis factor-α(TNF-α)and interleukin-10(IL-10) were detected,and the clinical curative effects were observed. Results Compared to the mosapride citrate treatment group,the total effective rate was significantly higher in the carbachol treatment group on the 7th day after treatment〔70.3%(26/37)vs. 45.5%(15/33),P<0.05〕. The activity of DAO,expression rates of CD11b+and CD18+in PMN,contents of TNF-αand IL-10 in the carbachol treatment group were decreased with the extension of time,and reached valley values on the 7th day,the differences were statistically significant in the comparisons with those in mosapride citrate treatment group at the same time point〔DAO(mg/L):3.21±0.52 vs. 3.93±0.51,CD11b+:(14.89±2.16)% vs.(28.92±1.59)%,CD18+:(53.67±2.44)% vs. (72.46±4.08)%, TNF-α(ng/L):111.44±16.42 vs. 129.73±18.74, IL-10(ng/L):67.71±38.83 vs. 121.45±40.23,all P<0.05〕. At the various time points,the above indexes had no obvious changes in mosapride citrate treatment group. Conclusion Carbachol can ameliorate the ischemic/reperfusion(I/R)injury in patients with intestinal barrier dysfunction after trauma,decrease the release of inflammatory cytokines in vivo,and promote peristalsis of intestinal tract,therefore carbachol has clinical value of protecting intestinal barrier function.
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Objective To observe the clinical effect of continuous intravenous pumping of octreotide in the treatment of intestinal endotoxemia.Methods Eighty patients with intestinal obstruction and non-surgical treatment were divided into group Ⅰ with 34 cases who received conventional-treatment and group Ⅱ with 46 cases who received conventional-treatment combined with octreotide 24 h continuous intravenous pumping.White blood cell count ( WBC ),diamine oxidase (DAO),D-lactic acid (D-LA) and endotoxin were detected before treatment and at 24 h,48 h,4 d after treatment.Results The content of WBC,DAO,D-LA and endotoxin in two groups all reached peak at 48 h after treatment.The difference of the content of WBC,DAO,D-LA and endotoxin between two groups had no statistical significance at 24 h after treatment (P ＞ 0.05).The content of WBC,DAO,D-LA and endotoxin of group Ⅱ at 48 h and 4 d after treatment were lower than those of group Ⅰ.And the difference at 48 h after treatment had statistical significance[(18.40 ±0.10)× 109/L vs.(20.60 ± 2.36) × 109/L,(6.12 ± 1.02) kU/L vs.(8.02 ± 1.54) kU/L,(2.14 ±0.21) mg/L vs.(3.34 ± 0.04) mg/L,(1.65 ±0.16) kEU/L w.(2.23 ±0.36) kEU/L] (P ＜ 0.01).While the difference at 4 d after treatment had no statistical significance(P＞ 0.05 ).Body temperature at 48 h after treatment,gastrointestinal decompression capacity,anus exhaust time of group Ⅱ were (37.60 + 3.01 )℃,(320.00 ± 76.14) ml/d,(54.00 ± 0.94) h respectively,and they all were superior to those of group Ⅰ[(38.50 ± 2.21 ) ℃,(500.00 ± 80.32) ml/d,(68.00 ± 1.02) h] (P ＜0.01).Conclusions Continuous intravenous pumping of octreotide can effectively protect the intestinal mucosal barrier function,improve intestinal permeability,reduce the trmslocation of intestinal flora,inhibit the incidence and development of enterogenous endotoxemia.And it provides new evidence to support the clinioal application of octreotide in patients with intestinal endotoxemia.
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BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane-bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5％sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. RESULTS: The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P<0.01, P<0.05). The expression levels of TREM-1, IL-1β and TNF-α mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P<0.01, P<0.05). The expression level of TREM-1mRNA was positively correlated with IL-1β and TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-α mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS: The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-l might play an important role in the development of intestinal barrier dysfunction in rats with SAP.
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ObjectiveTo investigate the protection effect of bifidobacterial adhesin for intestine ischemia/reperfusion (I/R) injury on gut barrier function in rat.MethodsSeventy-two male SD rats were randomly divided into sham operation group (n =24), I/R model group (n =24) and pretreatment group of bifidobacterial adhesin (pretreatment group, n = 24).Six rats were anatomized at 6 h, 1 d, 4 d and 7d after inducing I/R model in each group, respectively.The pathological changes of the terminal ilea and the blood levels of TNFα, IL-6, IL-10, diamine oxidase (DAO), and the activity and content of D-lactic acid were observed.ResultsThe blood levels of TNFα, IL-6, DAO and D-lactic acid in I/R model group were significantly higher than sham operation group at all time points (P ＜0.05) , while the blood level of IL-10 was no significantly change.The activity of IL-6 and DAO in pretreatment group was significantly lower than I/R model group at all time points (P ＜ 0.05), the blood level of TNFαt in pretreatment group was significantly lower than I/R model group at 1 d, the blood level of D-lactic was significantly lower than I/R model group at 4 d and 7 d (P ＜ 0.05). Intestinal pathological damages were obviously milder in pretreatment group than I/R model group at all time points (Chiu's pathological scores: 6 h, 3.22 ±0.22 vs 3.57 ±0.20;1 d,3.77 ±0.13 vs 3.90 ±0.12;4 d,2.93 ±0.23 vs 3.07 ±0.21;7 d,2.10 ±0.30 vs 2.22 ±0.17,all P ＜ 0.05).ConclusionThe pretreatment of bifidobacterial adhesin could protect the intestinal mucosa from I/R injury, and alleviate intestinal ischemic reperfusion injury.
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ObjectiveTo investigate the relationship between the expression of triggering receptor1 present on myeloid cells ( TREM-1 ) in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis (SAP). MethodsSixty-four male Wistar rats were randomly (random number) divided into sham operation group ( SO group, n = 32) and SAP group ( n = 32 ). The SAP model was established by retrograde injection of 5％ sodium deoxycholate into bile-pancreatic duct. Specimens from blood and intestinal tissue were collected 2, 6, 12 and 48 hours after modeling. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured with an modified spectro-photometric method. The expressions of TREM-1, IL-1β and TNF-αt mRNA in terminal ileum were detected by RT-PCR. All data were processed with SPSS version 16. 0 package to make one-way ANOVA and Spearman correlation analysis. ResultsThe serum levels of D-lactate, DAO and endotoxin were significantly increased at all intervals in SAP group compared with SO group ( P ＜ 0. 05 ). The expressions of TREM-1, IL-1β and TNF-α mRNA in terminal ileum of rats in SAP group at all intervals were significantly higher than those in SO group (P ＜ 0. 05 ). The expression of TREM-1 mRNA was positively correlated with expressions of IL-1 β and TNF-α mRNA ( r = 0. 956, P = 0. 044; r = 0. 986, P = 0. 015 ), but correlation was not found between expressions of IL-1β mRNA and TNF-α mRNA ( P = 0. 133 ). ConclusionsThe expression of TREM-1mRNA in intestinal tissue of rats with SAP is elevated, leading to the release of inflammatory cytokines and intestinal mucosal injury, indicating TREM-1 might play an important role in the genesis of intestinal barrier dysfunction in rats with SAP.
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Objective To observe the effects of vasedilator stimulated phosphoprotein (VASP) of small intestine mucous membrane on the intestinal barrier dysfunction during hemorrhagic shock (HS) in rats. Methods Forty Wistar rats were divided into normal group, HS 1 hour, HS 2 hours and HS 4 hours groups, as well as HS 2 hours + cyclic adenosine monophosphate (cAMP) treatment group. The activity of sermn diamine oxidase (DAO), content of hematoplasma D-lactic acid of each group were determined, and their relationship with the expression of VASP was analyzed. Results The expression of VASP was increased, serum DAO activity and hematoplasma D-lactic acid content were decreased by cAMP in rats at 2 hours after HS. There were differences upon the levels of VASP expression, DAO activity and hematoplasma D-lactic acid content between HS 2 hours group and HS 2 hours + cAMP treatment group ( t = 18.62, 9.28, 2.83, P < 0.05 ). The serum DAO activity increased while VASP expression decreased significantly after HS, which showed an obvious negative correlation between the two indexes (r=-0.95, P<0.05). Conclusions The decrease of VASP contributes to the intestinal barrier dysfunction after HS in rats, while the intestinal barrier dysfunction can be alleviated by cAMP.
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Objective To summarize the recent progress in pathogenetic,diagnostic and therapeutic researches on the intestinal barrier dysfunction(IBD) of severe acute pancreatitis(SAP).Methods The advancement of IBD in SAP,which was published recently at home and abroad,was collected and reviewed.Results The pathogenesis of IBD in patients with SAP was complex.Ischemia-reperfusion injury,endotoxin,inflammatory mediators and gastrointestinal hormone played an important role in the process of IBD.There were many ways to detect IBD,and the ratio of lactulose and mannitol,plasma diamine oxidase were relatively ideal markers.Medical therapies,such as treatment of SAP and maintaining the perfusion of intestines,were essential to cure IBD.On this basis,the propulsives,nutritional support and traditional Chinese drugs should be administered reasonably.Conclusions IBD is a sophisticated process of pathophysiology.In recent years,abundant of animal experiments and clinical researches have provided new clue for prevention and cure of IBD,but further researches are still needed on the mechanism of the cells and molecules implicated.