复合致病因素诱导大鼠肝硬化各脏器纤维化改变及机制

Multiple Organ Fibrosis in the Development of Liver Cirrhosis Induced by Mmultiple Pathogenic Factors in Rat and their Pathogenesis

目的:观察复合致病因素诱导的大鼠肝硬化形成过程中肺脏、肾脏、心脏的纤维化改变并探讨其发生机制。方法:将51只大鼠随机分为正常对照组、肝硬化模型4周组、6周组及8周组。采用复合致病因素法诱导大鼠肝硬化,分别摘取肝脏、肺脏、肾脏、心脏称重,计算各脏器系数;HE和VG染色分别观察各脏器损伤和纤维化情况;腹主动脉取血,测定血浆内毒素、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)和肿瘤坏死因子-α(TNF-α)水平;分别测定肝、肺、肾、心肌组织匀浆中TNF-α和丙二醛(MDA)水平。结果:模型各组血浆ALT活力、TBiL和TNF-α水平均高于对照组(P<0.05);血浆内毒素水平随病程进展逐渐升高,模型6周组及8周组明显高于对照组(P<0.05)。模型各组肝、肺、肾、心组织匀浆TNF-α、MDA水平随病程进展均逐渐升高并显著高于正常对照组(P<0.05)。各脏器组织纤维化指数均逐渐升高并显著高于正常对照组(P<0.05)。结论:肝硬化发病过程中,由肠源性内毒素引发的全身炎性反应,是导致各脏器发生纤维化的重要机制。

Objective：To observe multiple organ fibrosis and explore their pathogenesis in the development of liver cirrhosis induced by multiple pathogenic factors in rats.Methods：Fifty-one male Wistar rats were randomly divided into liver cirrhosis 4th week group,6th week group,8th week group,and normal control group.The rat model of hepatic cirrhosis was induced by multiple pathogenic factors to the animals.The organic coefficient of liver,lung,kidney and heart were determined.The organic injury and fibrosis were observed through the staining of HE and VG,respectively.Endotoxin,ALT,TNF-α,TBil,TNF-α in plasma,and TNF-α,MDA in organic tissue were detected.Results：With the development of liver cirrhosis,levels of endotoxin,ALT,TNF-α,TBil in plasma,and contents of TNF-α,MDA in organic tissue,and index of organic fibrosis were gradually increased and were significantly compared with normal control group in every model group（P0.05）.Conclusion：The systemic inflammatory response enlightened by ITEM may be involved in the pathogenesis of organic fibrosis in the development of liver cirrhosis induced by multiple pathogenic factors.