| Background and aims:Intestinal bacterial translocation (IBT) was one of the factors leading to spontaneous bacterial peritonitis (SBP) in liver cirrhosis. However, the major mechanisms concerning bacterial translocation in cirrhortics had not been completely clarified, although it had been showed that factors such as prolonged intestinal transit, increased intestinal permeability and intestinal bacterial overgrowth (IBO) were involved in development of IBT. Norfloxacin had been widely used in prevention of SBP in liver cirrhosis, but the development of resistant-species could lead to more severe IBT and SBP. It has been also reported that propranolol and Arobiotics may be helpful to IBT.Aims of the study were to: (1) understand in the incidence of IBT in experimental cirrhotic rats (2) explore the mechanisms of IBT in cirrhostics (3) evaluate effect of cisapride, lactulose and anti-sense tlr4 plasmid on IBT and intestinal mucosa of cirrhotic rats.Material and methods: Cirrhotic rats were induced by injection of 50% CCl4 solution subcutaneously for 12 weeks. Rats were divided into 7 groups, that is normal controls (n=25), cirrhotics (n=25), cirrhotic controls (n=20), cisapride group (n=20), lactulose group (n=20), norfloxacin (n=20) and antisense tlr4 plasmid group (n=20). All animals were assessed with following variables including IBT, IBO, serum endotoxin level, intestinal transit, intestinal permeability, pathological change and ultrastructure of ileum and tlr4 expression of intestine and liver.IBT was defined as positive culture of bacteria in the liver, spleen, mesenteric lymph node (MLN), blood and/or ascites. IBO was regarded to be bacteria number in jejunum more than mean value, plus 2 SD of normal rats. Serum endotoxin was determined by limulus ameobatic chromogenic assay. Intestinal transit was measured by 51Cr as geometric center ratio in intestine. Intestinal permeability was evaluated by urinary excretion of 99Tc-DTPA. Index of pathological change of ileum mucosa included villus height, villus height/width ratio, villi density and inflammatory index. Index of electronic microscopy included microvilli, tight junction and cell space. Expression of tlr4 in tissue were determined by RT-PCR and immune-biochemistry.Results: By comparing several variables obtained from measurement of intestinal transit with 51Cr, geometric center ratio or geometric center were showed better index than other two variables (intestinal distribution of 51Cr and leading edge ratio activity of intestine), 60 min in measurement interval was better than 30 min.24h urinary excretion of 99Tc-DTPA was not influenced by gastric emptying and intestinal transit. Intestinal permeability in cirrhotic rats was higher than normal and fibrotic rats, which was showed normal intestinal permeability.IBT and IBO were found 48% and 80% respectively in cirrhotic rats and none in control rats. Urinary excretion of 99Tc-DTPA in cirrhotic rats (16.1±7.6%) was higher than normal rats (1.62±0.8%), and in cirrhotic rats with BT (22.2±7.8%) was greater than those without BT (10.5±2.9%). Intestinal transit (geometric center ratio) was significantly delayed in cirrhotic rats (0.31±0.06) and further more delayed in cirrhotic rats with BT (0.24±0.06) than those without BT (0.38±0.11). Cirrhotic rats with IBO had significantly higher rates of bacterial and endotoxin translocation, slower intestinal transit and higher intestinal permeability than those without IBO. The same organism was always found at the same time both in IBT and IBO. All of the tested variables including IBO, IBT, intestinal permeability, intestinal transit and serum endotoxin were improved after treatment of cisapride, lactulose and norfloxacin. Tlr4 was rarely expressed in the intestine of normal rats but up-regulated in the intestine and down-regulated in the liver of cirrhotic rats. Tlr4 expression was greatly down-regulated in the liver after treatment. In cirrhotic rats, intestinal villi were injured including ruptured and shortened villi, decreased height/width ra...
|
PDF Full Text Request