一氧化氮、内皮素-1和肝“筛”在鼠淤胆性肝纤维化中的作用

Effects of nitric oxide,endothelin-1, and liver sieve on biliary fibrosis in rats

目的 探讨一氧化氮 (NO )和内皮素 1(ET 1)在淤胆性肝纤维化中的作用。方法 将 48只Wistar大鼠随机分成 :对照组、胆总管结扎组及胆总管结扎加乳果糖组。观察术后第 3 ,7,14和 2 1d血浆内毒素 ,NO和ET 1水平及肝脏结构和功能的变化。 结果 胆总管结扎致胆汁淤积后 ,随着血浆内毒素水平升高 ,NO和ET 1水平相应上升 ,血浆AST ,ALT也明显升高。肝纤维化程度随梗阻时间逐渐加重。电镜下见肝窦变窄 ,Disse间隙增宽 ,内有大量胶原纤维沉积 ,肝“筛”的数量和直径均明显减少。使用乳果糖能部分逆转肝脏功能和结构的病理改变。结论 NO和ET -1可能通过作用于肝“筛”而引起淤胆性肝纤维化。

Objective To study the effects of nitric oxide (NO) and endothelin-1(ET-1) on cholestasis liver fibrosis. Methods Forty-eight Wistar rats were randomily divided into 3 groups:the control group,the common bile dute ligation(CBDL)group,and the CBDL plus lactulose group.The animals were killed on the 3rd,7th,14th, and 21th days respectively to determine the contents of plasma endotoxin,NO,ET-1, and transaminases(ALT,AST).The degree of hepatic fibrosis was observed by microscopy and the ultrastructural changes of liver were observed by electron microscope. Results After common bile dute ligation,the contents of plasma ET-1 and NO increased significahtly,the plasma endotoxin level also increased and there were positive correlation between the levels of ET-1,and NO and the level of endotoxin.Plasma transaminases also increased greatly compared with those of the control group.The hepatic sinusoidal steonsis and widen Disse space were found.The diameter and number of fenestrate on hepatic sinusoid greatly decreased.Treatment with lactulose could partially alleviate all the pathological changes noted above. Conclusions NO and ET-1 may damage the 'liver sieve'to cause the cholestasis liver fibrosis.