ObjectiveTo investigate the effect of Lactobacillus plantarum (LP) on the intestinal barrier function under inflammation. MethodsInterleukin-10 knockout (IL-10－/－) mice were used as the model of inflammatory bowel disease. IL-10－/－ and wild type (WT) mice received the LP or Ringer solutions for 4 weeks. Colitis was assessed by histological score and clinical manifestation was observed. The gut paracellular permeability was measured by Ussing chamber. The concentrations of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected by the ELISA method. The expressions and distributions of tight junction proteins were determined by Western blot and immunofluorescence, respectively. ResultsCompared with the WT group, the diarrhea, rectal prolapse, and weight loss were obvious (Plt;0.01), the concentrations of TNF-α and IFN-γ significantly increased (Plt;0.01), the infiltration of numerous inflammatory cells, even transmural ulcers, and crypt abscess were observed, the ultrastructure of tight junction was damaged, the mannitol permeability significantly increased (Plt;0.001) and transepithelial resistance (TER) significantly decreased (Plt;0.001), and the expressions of tight junction proteins (ZO-1, occludin, and claudin-1) significantly decreased (Plt;0.01) in the IL-10－/－ group. Compared with the IL-10－/－ group, the clinical and pathological manifestations of colitis significantly improved (Plt;0.01), the ultrastructural damage of tight junction was prevented, the mannitol permeability significantly decreased (Plt;0.001) and the TER significantly increased (Plt;0.001), the concentrations of TNF-α and IFN-γ significantly decreased (Plt;0.01), and the expressions of tight junction proteins (ZO-1, occludin, and claudin-1) significantly increased (Plt;0.01) in the IL-10－/－+LP group. ConclusionTreatment with LP ameliorates colonic epithelial barrier dysfunction by promoting the expressions of tight junctional proteins in IL-10－/－ mice.
Objective To investigate the effects of N-acetylcysteine （NAC） on the intestinal barrier in rats with severe acute pancreatitis （SAP） and its possible mechanism. Methods Eighty Wistar rats were randomly （random number method） divided into normal control group （CON group， n=8）， sham operation group （SO group， n=24）， SAP group （n=24）， and NAC group （n=24）， then the rats of latter 3 groups were sub-divided into 6， 12， and 24 hours group， each time point group enrolled 8 rats， respectively. Rats of CON group didn’t receive any treatment. SAP rat models were established by injecting 5.0% sodium taurocholate into the biliary-pancreatic duct for SAP group and NAC group， while rats of SO group were injected normal saline instead of sodium taurocholate. The rats of NAC group were given an intraperitoneal injection of NAC at 1 hour before operation， and the rats of SO group and SAP group were given an intraperitoneal injection of normal saline instead at the same time. Rats of CON group were sacrificed to get ileum （about 5cm） and blood from right ventricular （5mL） for further test， and rats of the other 3 groups were sacrificed at 6， 12， and 24hours after operation. Then the levels of amylase （AMY）， C-reactive protein （CRP）， endotoxin， D-lactic acid， and diamine oxidase （DAO） in plasma， the levels of superoxide dismutase （T-SOD）， myeloperoxidase （MPO）， and malondialdehyde （MDA） in ileum tissues were tested. Apoptosis of mucosal cells in ileum tissues was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL）. Pathological changes in ileum tissues were observed and scored. Expression levels of bax and bcl-2mRNA in ileum tissues were determined by real-timefluorescence quantitative PCR （real-time PCR）， and related proteins were tested by Western blot method， respectively. Results Compared with SAP group at the same time point， the levels of CRP in NAC group were lower at all the 3 time points （P＜0.05） and AMY were lower at 12 and 24 hours （P＜0.05）， levels of DAO， endotoxin， and D-lactic acid were lower at 12 and 24 hours （P＜0.05）， but level of DAO was higher than SAP group at 6 hours （P＜0.05）. Compared with SAP group at the same time point， the levels of MPO and MDA in ileum tissues were lower in NAC group at all the 3 time points （P＜0.05）， but levels of T-SOD increased significantly at 12 and 24 hours （P＜0.05）. Compared with SAP group at the same time point， the apoptosis indexes were lower in NAC group at all the 3 time points （P＜0.01）， and pathologic scores of ileum tissues were lower at 12 and 24 hours （P＜0.05）. The pathological changes under a light microscope were observed better in NAC group than that of SAP group at each time point. Moreover， compared with SAP group at the same time point， the expression levels of bax mRNA and protein were lower in NAC group at all the 3 time points （P＜0.05）， while higher in bcl-2 mRNA and protein （P＜0.05）. Conclusions NAC can protect the function of small intestinal barrier， and can alleviate SAP-induced injury of the intestinal mucosa. In addition to antioxidant effects， the underlying mechanisms also may include the anti-apoptotic effects.
Objective To investigate the protective effects and the mechanism of recombinant human growth hormone on the intestinal barrier function. Methods The literatures of recent years were reviewed and summarized． Results The recombinant human growth hormone not only prevent mucosal cells and immunological cells from apoptosis, but also antagonize the damage of NO, cytokines, as well as endotoxin on intestinal barrier. What’s more, it increases the intestinal uptake and utilization of glutamine. All of the above could maintain the integrity and functions of the intestinal barrier. Conclusion The recombinant human growth hormone protects the intestinal barrier function through different ways.
Objective To summarize the recent progress in pathogenetic, diagnostic and therapeutic researches on the intestinal barrier dysfunction (IBD) of severe acute pancreatitis (SAP). MethodsThe 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.
Objective To observe the influence of “liqitongxia decoction” on intestinal barrier dysfunction of acute pancreatitis (AP). Methods Forty AP patients were randomly divided into “liqitongxia decoction” group (n=20) and magnesium sulfate group (n=20). APACHE Ⅱ score and gastrointestinal functions score (GFS) on admission， at 24 h, 48 h, 72 h and on day 5 after admission were recorded. The ratio of urine lactulose to mannitol (L/M), plasma activity of diamine oxidase (DAO) and the levels of endotoxin, TNF-α and IL-6 on admission, at 72 h and on the day 5 after admission were detected. Results The ratio of severe AP was not significantly different between two groups (P＞0.05). On the day 5 after admission, APACHEⅡscore and GFS in two groups decreased. The ratio of L/M, the activity of DAO, the levels of endotoxin, TNF-α and IL-6 decreased in “liqitongxia decoction” group and elevated in magnesium sulfate group. The APACHE Ⅱ score was not significantly different between two groups on the day 5 of admission (P＞0.05), but the GFS, the ratio of L/M, the activity of DAO, levels of endotoxin, TNF-α and IL-6 were significantly different between two groups (P＜0.05, P＜0.01). Conclusion The “liqitongxia decoction” may ameliorate the intestinal barrier dysfunction of patients with acute pancreatitis.
Objective To study the effect of probiotics on the change of intestinal permeability and inflammatory reaction after surgery of colorectal cancer. Methods Sixty patients who underwent colonic surgery were randomly divided into two groups: probiotic group and control group, with 30 cases in each group. Each group received nutritional support of the same nitrogen and calorie from day 3 to day 7 after operation. The patients in probiotic group were orally administrated probiotic (2 g/d) from the first day after surgery for 7 days. Every patient’s body temperature and heart rate were observed after operation, and white blood cell counts were observed before operation and on day 1, 5, 8 after operation. The levels of microbial DNA in whole blood and plasma D-lactate, and urine lactulose/mannito (L/M) ratio were measured before operation and on day 1 and day 8 after operation, respectively. In addition, the occurrence of postoperative systemic inflammatory response syndrome (SIRS) and complications of inflammation were closely observed. Results The average heart rate in postoperative 5 days was significantly lower in probiotics group than that in control group (P＜0.01). The duration of fever and the recovery time for white blood cell counts decreasing to normal were significantly less in probiotics group than those in control group (P＜0.01) as well. There was no significant difference of positive rate of microbial DNA in peripheral blood on day 1 after operation between two groups. However, the number of patients that showed positive result of microbial DNA PCR test in probiotic group （1 case, 3.3%） was significantly less than that of control group (7 cases, 23.3%）on day 8 after operation (P＜0.05). The level of plasma D-lactate in probiotic group 〔decreasing from (6.90±1.41) ng/ml on day 1 to (0.56±0.18) ng/ml on day 8〕 was also significantly lower than that in control group 〔decreasing from (6.63±1.29) ng/ml on day 1 to (0.95±0.83) ng/ml on day 8〕 on day 8 after operation (P＜0.05). Urine L/M ratio increased from 0.053±0.019 on day 1 to 0.063±0.016 on day 8 after operation in control group; while in probiotic group, the ratio decreased from 0.047±0.012 on day 1 to 0.031±0.008 on day 8 after operation, and there was significantly statistical difference of the ratio between two groups on day 8 (P＜0.01). There was no significant difference of the occurrence rate of SIRS and complications of inflammation between two groups (Pgt;0.05). Conclusion Probiotics can decrease intestinal permeability and maintain the intestinal barrier function after operation. It may be helpful for the recovery of patients with early inflammatory response after surgery of colorectal cancer.
【Abstract】ObjectiveTo review the research advance of intestinal barrier changes and its pathogenesis in stress conditions.MethodsThe literatures in recent years on the changes of the intestinal barrier,and its pathogenesis in stress conditions were reviewed.Results In some severe stress conditions, such as trauma, severe inflammation and acute severe pancreatitis, etc, a series of pathophysiologic disorders of intestinal barrier， even systemic inflammatory response syndrome and multiple organ dysfunction syndrome or multiple organ failure were induced. The pathogenesis was a result of a series of neurologic, immunologic and endocrine factors making one another. ConclusionRecognizing the changes and pathogenesis have an important clinical significance for treating and preventing the intestinal barrier dysfunction induced by stress.
The gut mucus barrier and mechanical barrier are the most important natural barriers, the former is the first defense barrier, which separates pathogenic bacteria in intestinal lumen from the epithelial cells, and prevents them passing through the intestinal barrier into the human circulation system. Studies have shown that inflammation in the body affects the content of mucin 2, a key protein in the mucus layer, thereby changing the permeability of the mucus barrier and promoting the translocation of pathogenic microorganisms. Both tumor necrosis factor-α and c-jun N-terminal kinase signaling pathways have been reported to be closely related to the occurrence and development of inflammation. Therefore, this article reviews the relationship between tumor necrosis factor-α, c-jun N-terminal kinase signaling pathway and mucin 2 and intestinal barrier dysfunction, in order to provide new ideas and directions for exploring the related research of intestinal barrier function.