Effects Of Bile Acids On Intestinal Bacterial Overgrowth, Bacterial Translocation And Endotoxemia In Cirrhotic Rats

Bacterial translocation is described as the passage of viable gut flora and it's products such as endotoxin and bacterial DNA across the intestinal barrier to extraluminal sites,which would be intestinal framework, mesenteric lymph nodes, portal vein and some other organs and/or systems. Delayed intestinal transit,intestinal bacterial overgrowth, impairment of the intestinal mucosal barrier, and waking of local host immunity are the major mechanisms postulated to favour bacterial translocation in cirrhosis.Then bacterial translocation promotes the development of bacteraemia and spontaneous bacterial peritonitis in cirrhosis.The main measures to prophylax or treat bacterial translocation in cirrhosis include adjusting the various intestinal flora ratio,selective intestinal decomtamination,enhancing intestinal transit,et al.But their defective effects on prophylaxis of bacterial translocation limit their clinical application.Bacterial translocation is not a "all or none" process. So inhibiting intestinal bacterial overgrowth is the key factor for prophylaxis or treatment of bacterial translocation.The effect of bile salt inhibiting the growth of bact has been demonstrated in cirrhotic rats and cirrhosis.The bile secretion is lower in cirrhosis than that in health.The supplement of bile acid can increase the secretion of bile and inhibit intestinal bacterial overgrowth effectually in cirrhosis.Aim: 1.To observe the incidence of bacterial translocation in cirrhotic rats and the routes that the translocated intestinal flora pass through.2.To approach the relationship between bile acid and intestinal flora and it's effect on bacterial translocation and endotoxin in serum by surveying the rate of bile secretion,the amount of intestinal bacteria and the plasma endotoxin level in ascitic cirrhotic rats.3.To evaluate the effects of conjugated or unconjugated bile acids on the rate of bile secretion,amount of intestinal bacteria,the incidence of intestinal bacterial translocation,and endotoxemia in ascitic cirrhotic rats by administrating urosodeoxycholic acid and cholyglycine.Try to find a new strategy and therapy for prophylaxing intestinal bacterial translocation in ascitic cirrhotic rats.Methods:37 cirrhotic rats with ascites (ascites was documented by ultrasonography)induced by CC14 and 30 healthy rats were utended in the experiment. 1 .At the end of the treatment period all rats underwent laparotomy in an unfastened state,which was performed under general anesthesia and aseptic conditions.The common bile duct was identified and cannulated with a small polyethylene catheter.Bile was collected for 30 minutes for measurement of biliary secretion rate.Samples for culture were harvested in the following order.ascitic fluid, lymph fluid in pars abdominalis ductus thoracici, systemic venous blood(suprahepatic inferior vena cava),portal venous blood, systemic arterious blood(abdominal aorta),from which 2ml of each was taken;mesenteric lymph nodes(3 of them,particularly those draining lymph from ileum and cecum);and a section of liver and spleen. The terminal ileum was identified and the ileal content was obtained. 2.37 cirrhotic rats and 30 rats in contrast were divided into 3 subgroups,one of which received urodeoxycholic acid(UDCA),cholyglycine(CG)(both at 70mg/kg/d),and placebo respectively.All animals were treated for 2 weeks.At the end of treatment,the rate of bile secretion,total bacteria in ileum,the incidence of bacterialtranslocation,and plasma endotoxin level in ascitic cirrhotic rats and healty rats were detected.Results: l.The incidence of bacterial translocation in cirrhotic rats and the route that the translocated intestinal flora pass through. About 67% of the cirrhotic rats occurred bacterial translocation.The positive rate of cultured lymph fluid in pars abdominalis ductus thoracici and mesenteric lymph nodes was higher than that in portal venous blood and systemic venous blood(suprahepatic inferior vena cava).No bacterial translocation was observed in the 30 rats in contrast. 2.The relationship among the rate of bile secretion,intestinal content,and intestinal bacterial tranclocation.The rate of bile secretion in cirrhotic rats was significantly lower than healthy rats(P <0.001).The amout of intestinal bacteria in ascitic cirrhotic rats was significantly higher than that in healthy rats(P<0.001). Negative correlation was showed between the rate of bile secretion and total ileal bacterial content in cirrhotic rats.The incidence of bacterial translocation and plasma endotoxin level in cirrhotic rats were significantly higher than those in contrast group(P<0.001). Negative correlation was observed between the rate of bile secretion and total ileal bacterial content in cirrhotic rats.The same results were received in the rate of bile secretion and bacterial translocation and plasma endotoxin level in cirrhotic rats.However,there appeared positive correlation between the amount of terminal ileal bacteria and bacterial translocation in cirrhotic rats,and the same result was obtained in amount of terminal ileal bacteria and plasma endotoxin level in cirrhotic rats.3. The effects of bile acid on the incidence of intestinal bacterial translocation and endotoxemia in ascitic cirrhotic rats.Bile secretion rate was significantly higher in cirrhotic rats received bile acids than that in rats received placebo(P<.001),and bile acids administration in cirrhotic rats normalized bile secretion. The conjugated bile acid and unconjugated bile acid had similar effects.The amount of terminal ileal bacteriawas significantly lower in cirrhotic rats received bile acids than that in received placebo(P<.001).Bile acids administration in cirrhotic rats reduced total ileal bacterial content to normal level.The rate of bacteriala translocation and plasma endotoxin level were significantly lower in cirrhotic rats given bile acids than those in rats given placebo(P<.001),but the survival rate was significantly greater in rats received bile acids. Though the incidence of bacterial translocation was decreased significantly in cirrhotic rats received bile acids,the positive rates of cultured lymph fluid in pars abdominalis ductus thoracici and mesenteric lymph nodes were significantly higher than those of portal venous blood and systemic venous blood(suprahepatic inferior vena cava).Conclusions: l.The incidence of bacterial translocation in cirrhotic rats was higher than that in healthy rats.The main route that translocated intestinal flora passing through was from mesenteric lymph nodes to pars abdominalis ductus thoracici,and then to systemic circulation. 2.The rate of bile secretion in cirrhotic rats was significantly lower than that in contrast group.Intestinal bacterial overgrowth,bacterial translocation,and endotoxemia occurred in most of the cirrhotic rats. 3.Bile acids administration increased bile secretion,mhibited intestinal bacterial overgrowth,decreased the rate of bacterial translocation and plasma endotoxin level.The administration of conjugated bile acid and unconjugated bile acid achieved similar effects.