内毒素血症在大鼠肝硬化发生发展中的作用

目的:探讨内毒素血症在大鼠肝硬化发生发展过程中的作用。方法:采用饮水中加入硫代乙酰胺(TAA),另一组同时小剂量注射脂多糖(LPS),以观察其对肝硬化形成的影响。结果:TAA可使动物血浆内毒素水平与肝脏胶原蛋白含量明显增高,且二者存在直线相关;血浆和肝组织中肿瘤坏死因子α(TNFα)、内皮素-1(ET-1)、一氧化氮(NO)、丙二醛(MDA)含量均增加,而且血浆中各成分含量均与内毒素血症呈正相关;在TAA+LPS组动物唯有TNFα浓度和胶原蛋白含量明显高于TAA组。结论:在肝硬化形成过程中内毒素可能主要通过激活枯否细胞分泌TNFα发挥其作用,但ET-1、NO和自由基也参与其中。

Role of endotoxemia in the occurrence and development of cirrhosis

AIM: To study the roles of endotoxemia in the occurence and development of cirrhosis. METHODS: The cirrhosis of rats were made by oral intake of thioacetamide (TAA-treated rats). A separate group of rats were subjected to a injection of small dosage of lipopolisaccharride (LPS) in the period of thiocetamide treatment in order to observe the possible effect of LPS on the forming of cirrhosis. RESULTS:Both plasma endotoxin levels and hepatic collagen contents were increased in TAA-treated rats,and there was a linear correlation between them ;Plasma and hepatic tumor necrosis factor (TNFα)、endothelin-1(ET-1)、nitric oxide(NO)、and MDA levels were all increased,and plasma endotoxin was correlated with all of their plasma contents;Only TNFα levels and hepatic collagen contents of TAA+LPS group were increased significantly compared with TAA group. CONCLUSION: These results suggest that endotoxemia (ETM) could play an important role in the development of cirrhosis mainly through activating Kupffer cells, which secrete TNFα, ET-1, NO and free radicals could be involved in the process.