Basic And Clinical Study On Endotoxin Level And Intestinal Barrier Function With Progressive Fibrosis

Part I:Relationship between intestinal barrier function of small intestinal mucosa and plasma endotoxin in chronic liver damage ratObjective:To establish the models of rats with chronic liver damage.To explore the morphological structure changes of small intestinal mucosa and plasma endotoxin in rats with chronic liver;and explore its pathogenesis by examining and comparing the distribution and quantity of interstitial cells of cajal(ICC)in. the intestinal tract of normal and model rats by immunohistochemical study.Methods:twenty-four female SD(Sprague-Dawley) rats were randomly divided into normal control group and model group.The latter group of rats were intraperitoneally injected with thioacetamide (TAA)-physiologic saline, two times per week.The former group of rat were intraperitoneally injected with physiologic-saline,two times per week,served as controls.The rats to be put to death at the eight weekend.To observe the condition of liver fibrosis and the intestinal mucosa pathology both in normal and model rats by HE staining.Morphological structure changes of small intestinal mucosa were observed by light microscopy and transmission electron microscopy and plasma endotoxin in the abdominal aorta was measured with limilus lysate test;we observed the clinical manifestations of rats Immunohistochemical study was used to examine and compare the distribution and quantity of interstitial cells of cajal in the colon tissue of normal, and model rats.Results:(1)When compared with the normal control group:liver fibrosis of the liver tissue was existed in model rats;(2)Small intestinal villi of the model group in cirrhotic rats were injured under light microscopy,including reduced and atrophyed microvilli on the cells of intestinal mucosa.necrosis of the epithelial cell.and mucosal swelling with infiltrating of inflammatory cell.Ultrasturctural changes of small intestinal mucosa occurred in the model group under electronic microscopy,including injured microvilli,wider gap of tight junction and the tumefaction of mitochondrion and endoplasmic reticulum.But there were no obvious changes in normal rats;(3)Plasma endotoxin level of model rats was significantly higher than the normal control group(P<0.01);(4)Compared with the normal control group.ICCs were not well-distributed,the number of ICCs in some area increased but decreased in other area(positive cells were control group,P<0.01)..Conclusions:(1)Rat liver fibrosis model induced by TAA is established successfully. It is suggested that cirrhotic rats have significantly changed morphological structure and higher plasma endotoxin.The injury of small intestinal mucosa may be closely related with intestinal endotoxemia in chronic liver damage;(2)The loss of ICC may play a key role in the pathogenesis of intestinal barrier dysfunction in rats with chronic liver damage. Relationship between plasma endotoxin level and Child-pugh classification in patients with liver cirrhosis.Objective:To evaluate the association between the Child-pugh classification and plasma endotoxin level in patients with liver cirrhosis.Method:30patients with hepatitis B cirrhosis were collected from Nov2010to Feb2011as the study object and30healthy subjects entered this study.Plasma endotoxin in the Peripheral blood was measured with limilus lysate test and the relationship between Child-pugh classification and plasma endotoxin was assessed.Results:(1)The plasma endotoxin levels were significantly higher in cirrhosis patients than in healthy subjects(P<0.01);(2)Plasma endotoxin levels were comparable between cirrhosis patients with Child-pugh class A and B (P>0.05),The plasma endotoxin levels were significantly higher in cirrhosis patients with Child-pugh class C than Child-pugh class B(P<0.05);(3)A linear correlation was observed between plasma endotoxin levels and Child-pugh score(r=0.475,P<0.01)Conclusion:Endotoxemia is common in patients with liver cirrhosis,plasma endotoxin is significantly correlated with Child-pugh classification.