Objective To explore the protective effect of early enteral nutrition on intestinal mucosa barrier in patients with esophageal carcinoma after operation. Methods Fifty six patients with esophageal carcinoma whose weight decreased more than 20% before operation in three months were divided into enteral nutrition group ( n =30) and parenteral nutrition group ( n =26). Plasma concentration of lipopolysaccharide(LPS), tumor necrosis factor (TNF), gastrin, glutamine, and ratio of lactulose and mannitol (L/M) were measured on the 1st, 4th, 8th day after operation respectively. Results Weight loss and infectious complication in enteral nutrition group were less than those in parenteral nutrition group after operation ( P lt;0.01, 0.05). On the 4th and 8th day after operation,the level of LPS,TNF, and L/M were lower in enteral nutrition group than those in parenteral nutrition group ( P lt;0 01), the values of gastrin and glutamine were higher in enteral nutrition group than those in parente...更多ral nutrition group ( P lt;0 01). Conclusion Enteral nutrition can protect the intestinal mucosa barrier and decrease infectious complication after operation.
【摘要】 目的 探讨NF-κB在重症急性胰腺炎小鼠肠黏膜屏障功能损伤中的调控机制。 方法 36只BALB/C小鼠随机分为对照组、模型组、NF-κB干预组，每组12只。18 h后处死小鼠，比较各组的腹腔内大体改变、肠黏膜病理改变，肠道通透性的变化及血清细胞因子水平，肠上皮紧密连接蛋白occludin的表达。 结果 模型组小鼠腹腔内呈明显炎症反应，肠管水肿，肠黏膜水肿，肠道通透性显著增高，NF-κB特异性阻断剂能降低肠道损伤，改善肠黏膜水肿，上调肠上皮紧密连接蛋白occludin的表达，显著降低肠道通透性，降低细胞因子水平。 结论 NF-κB阻断剂能够通过选择性的抑制NF-κB活性，改善受损的肠屏障功能。这一作用通过上调肠上皮紧密连接蛋白occludin的水平而实现。【Abstract】 Objective To investigate the roles of NF-κB in the intestinal mucosal barrier injury in mice with severe acute pancreatitis(SAP). Methods Thirty-six BALB/C mice were randomly assigned to normal control group, SAP model group and intervention group. Eighteen hours later, pathological intestinal villus changes, intestinal permeability, serum cytokines were evaluated in all three groups. Results In SAP model group, intestinal mucosa was found to be oedematous and intestinal permeability was markedly increased. NF-κB could ameliorate intestinal injury and mucosa edema, and improve intestinal permeability by upregulating occluding expression. Conclusion NF-κB could protect the function of intestinal mucosal barrier by inhibiting NF-κB activity, which suggests that NF-κB may play an intermediating role in SAP-induced intestinal failure through upregulating occluding expression.
Objective To study the effect on expression of high mobility group box-1 （HMGB1） mRNA for the expression of zonula occludens-1 （ZO-1） in ileum tissues， and to explore the possible mechanism of intestinal mucosal barrier injury in rats with acute necrotizing pancreatitis （ANP）. Methods Ninety-six male Wistar rats were divided randomly （random number method） into ANP group， ethyl pyruvate （EP）group， and sham operation group. Eight rats of 3 groups were killed to get abdominal aortic blood and ileal tissues at 6， 12， 24， and 48h after operation， respectively.The levels of plasma amylase （AMY） ， D-lactate acid， and the activity of malonyl dialdehyde （MDA） in the ileum tissues were determined by using automatic biochemical analyzer， improved enzymatic spectrophotometry， and thiobarbituric acid （TAB） colorimetry respectively. The pathological changes of ileum tissues were observed under microscopy by HE staining， the expression of ZO-1 protein in ileum tissues was observed by immunohistochemistry （SP method）， and the expressions of HMGB1 mRNA and ZO-1 mRNA in ileum tissues were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared with ANP group at the same time， levels of AMY， D-lactate acid， and MDA in ileum tissues of EP group were all significantly lower （P＜0.05）. The expression level of HMGB1 mRNA increased at 6 h while ZO-1 mRNA decreased in ANP group. Compared with ANP group at the same time， the expression level of HMGB1 mRNA of EP group was significantly lower while ZO-1 mRNA was higher （P＜0.05）， and the pathological damage in ileum tissues was lighter. Conclusions The decreased expression of ZO-1 in ileum tissues is one of the vitalcauses for intestinal mucosal barrier injury in ANP， and it probably occurs in case of the excessive expression of HMGB1.
ObjectiveTo study the expression of zonula occluden-1 (ZO-1) in ileum tissues and the possible mechanism of intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). MethodsFifty SD male rats were randomly divided into sham operation group and SAP group, then SAP group was divided into four subgroups with 10 rats in each subgroup according to the sampling time of 3, 6, 12, and 24 h. The SAP model was made by injecting 5% bovine sodium deoxycholate into biliarypancreatic duct with Aho’s method. The rats were killed at 3, 6, 12, and 24 h after making model. The rats in the sham operation group were killed directly. Tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), and histological changes in pancreatic and intestinal pathologies were observed. At the same time, the ZO-1 protein and mRNA expressions of ileum tissues were detected by immunohistochemistry and RT-PCR, respectively. ResultsCompared with the sham operation group 〔TNF-α: (10.83±0.96) ng/L; DAO: (354.79±3.67) U/L; ZO-1 protein: (10.40±0.45) score; ZO-1 mRNA: 0.878±0.014 8〕, the levels of TNF-α at different time 〔3 h: (125.30±0.94) ng/L; 6 h: (181.89±4.93) ng/L; 12 h: (230.58±1.28) ng/L; 24 h: (198.89±4.83) ng/L〕 were significantly higher (Plt;0.05), the activities of DAO 〔3 h: (235.77±0.67) U/L; 6 h: (117.22±5.58) U/L; 12 h: (106.69±1.39) U/L; 24 h: (91.18±1.09) U/L〕 were significantly lower (Plt;0.05), ZO-1 protein 〔3 h: (8.70±0.22) score; 6 h: (3.73±0.19) score; 12 h: (3.92±0.22) score; 24 h: (4.29±0.30) score〕 and mRNA (3 h: 0.806±0.020 7; 6 h: 0.370±0.015 8; 12 h: 0.502±0.019 2; 24 h: 0.562±0.030 3) expressions of the ileum tissues were significantly lower (Plt;0.05) in the SAP group; Meanwhile, the necrosis of ileum mucous membrane chorioepithelium, angiorrhexis and hemorrhage, and inflammatory cell infiltration in the pancreatic and ileum tissues were also observed. ConclusionThe decrease of expression of ZO-1 in ileum tissues is one of the vital causes for mucosal barrier injury in SAP, probably through acts the excessive release of inflammatory cytokines TNF-α and the decrease of DAO activity.
Objective To investigate the effects and mechanisms of bile on small intestine mucosal barrier.Methods Fifty Wistar rats were assinged into 3 groups randomly: obstructive jaundice (OJ) group （n=20）, biliary external drainage group （n=20） and control group （n=10）. Ten days after operation, the plasma endotoxin level was determinated, the terminal ileum mucosas was obtained to be morphologically measured by light microscope, and immunohistochemistry and Western blot were uesd to examine the expressions of tight junction proteins zona occludens-1 (ZO-1) and occludin in the mucosas. Results Atrophy significantly appeared in the distal ileum mucosas in OJ group. Compared with control group, the intestinal villus height, mucosa thickness and crypt depth in OJ group were obviously decreased 27.8%, 21.7%, and 25.4% (P=0.001, 0.001, 0.040). There were no differences between external drainage group and control group (P=0.050, 0.070, 0.080); While the values of external drainage group were significantly higher than those in OJ group (all P=0.001). The level of plasma endotoxin was up to (1.49±0.27) EU/ml in OJ group compared with control group 〔（0.27±0.09） EU/ml〕, P=0.001. In external drainage group, the value was （0.91±0.25） EU/ml, which was obviously higher than that in control group and lower than that in OJ group （all P=0.001）. Immunohistochemical study showed b positive expression of ZO-1 dropped from 7/10 in the control group to 6/20 in OJ group （P=0.040）, occludin expression was 8/10 in control group and 7/20 in OJ Group （P=0.020）; expressions of them in external drainage group 〔8/20 （P=0.100,0.210） and 9/20 （P=0.060, 0.200）〕 displayed no significant differences compared with the other twogroups. Quantitative testing of Western blot showed the expressions of ZO-1 and occludin in OJ group were significantly lower than those in control group (P=0.001, 0.010), the values in external drainage group were higher than those in OJ group （P=0.005, 0.014）. The expression of ZO-1 was lower in external drainage group than that in control group (P=0.001), and there was no significant difference of occludin between the two groups (P=0.062）. Conclusion Lack of intestinal bile will undermine the intestinal tight junction protein composition, and make intestinal mucosal barrier impaired. The intestinal barrier more severely injured when biliary tract obstructs because of multiple factors. Bile plays an important role in the maintenance of intestinal mucosal barrier.
Objective To observe barrier function changes of gut mucosa in rats with acute respiratory distress syndrome(ARDS)．Methods Forty SD rats were randomized to an experiment group (n：30)and a control group(n=10)．Oleic acid was injected via vena femoralis to establish ARDS ratmode1．Subgroups in the experiment group were randomly divided by time 30 min，2 h，4 h interval after injection(n=10 in each subgroup)．Concentration of D-lactate and endotoxin and activity of diamineoxidase in blood plasma were measured．Histopathological changes of small intestine were observed under light microscope．Results Compared with the control group，the activation of diamine oxidase in the experiment group was higher after 30 min of injection(Plt;0.01)．Concentration of D-lactate，the activity ofdiamine oxidase and endotoxin level in the experiment group were all elevated after 2 hours of injection(all Plt;0.05)，and further elevated after 4 hours．In the rats’villous interstitial after 2 hours of the injection，there were edema，hyperemia，and infiltration of neutrophils，eosinophils and lymphocytes．After 4 hours ofthe injection，the villous epithelium showed desquamation，necrosis，denaturalization and erosion，associated with infihration of lymphocytes and neutrophils in the mucosa．Conclusion In oleic acid-induced ARDS．permeability of gut mueosa increases and gut barrier is dysfunctional．
This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n=10) and the experimental group (n=14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08±1.29, 11.04±7.55 and 12.21±4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72±3.58, P < 0.01), while the Lactobacillus number was decreased significantly (0.67±0.34, P < 0.01), and the Bifidobacterium number was also decreased (4.59±3.42, P < 0.05) in the experimental group, so the ratio of Bifidobacterium/Escherichia coli was reversed. Besides, in the experimental group, the plasma endotoxin positive rates and the bacterial translocation rates were much higher (P < 0.01 or P < 0.05) and the pathology scores of pancreas and small intestines were also significantly higher (P < 0.01) than those in the control group. These results indicated that in severe acute pancreatitis rats, the intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.
Objective To investigate the mechanism of bone morphogenetic protein-4 (BMP4) in promoting the recovery of small intestinal mucosal barrier function during the recovery period of small intestine ischemia-reperfusion (I/R) injury. Methods Twenty-eight C57BL/6J male mice aged 6–8 weeks were randomly selected and assigned to small intestine I/R group (n=24) and sham operation (SO) group (n=4) by random number table method. Small intestine I/R injury models of 24 mice were established, then 4 mice were randomly selected at 6, 12, 24 and 48 h after I/R established modeling and killed to observe the morphological changes of small intestinal mucosa and detect the expression of BMP4 mRNA in the jejunal epithelial cells, the other 8 mice were allocated for the experimental observation at the recovery period of small intestine I/R injury (24 h after I/R was selected as the observation time point of recovery period of small intestine I/R injury according to the pre-experimental results). Twelve mice were randomly divided into I/R-24 h-BMP4 group (recombinant human BMP4 protein was injected intraperitoneally), I/R-24 h-NS (normal saline) group (NS was injected intraperitoneally), and I/R-24 h-blank group (did nothing), 4 mice in each group. Then the small intestinal transmembrane electrical impedance (TER) was measured by Ussing chamber. The expressions of BMP4 protein and tight junction proteins (occludin and ZO-1), Notch signaling pathway proteins (Notch1 and Jagged1), and Smad6 protein were detected by Western blot. Results At 24 h after I/R injury, the injuries of villous epithelium, edema, and a small part of villi were alleviated. The BMP4 mRNA expressions at 6, 12, 24 and 48 h after I/R injury in the small intestinal epithelial cells were increased as compared with the SO group. Compared with the I/R-24 h-NS group and the I/R-24 h-blank group, the TER was increased, and the expression levels of occludin, ZO-1, p-Smad6, Notch1, Jagged1 were increased in the I/R-24 h-BMP4 group. Conclusion From the preliminary results of this study, during recovery period of small intestine I/R injury, the expression of BMP4 in small intestinal epithelial cells is increased, permeability of jejunal mucosal barrier is increased, which might promote the recovery of small intestinal mucosal barrier function by activating the Notch signaling pathway (Notch1 and Jagged1), Smad classic signaling pathway, and promoting the increase of tight junction protein expression (occludin and ZO-1).