阻塞性黄疸中肝细胞凋亡及机制的研究

Apoptosis as a Mechanism of Cell Death in the Liver of Obstructive J aundice.

目的:观察阻塞性黄疸中肝细胞凋亡,并进一步探讨其分子机制。方法:结扎Wistar大鼠胆总管建立阻塞性黄疸模型,应用普通组织学、原位末端标记方法检测阻塞性黄疸不同时期肝细胞凋亡,及解除梗阻后病理学和细胞凋亡的变化情况;采用ELISA、生物化学等方法检测血清胆红素、肿瘤坏死因子(TNF)鄄α、三酰甘油浓度;并应用免疫组化方法检测肝脏转化生长因子(TGF)鄄β1的表达。结果:大鼠胆总管结扎术后3天,即可见肝胆管扩张,细胞凋亡明显增多,早期随着胆红素升高,肝细胞凋亡数量与之呈正相关,后期纤维组织大量增生,肝细胞凋亡相对减少;解除梗阻后,细胞凋亡逐渐减少,直至正常。结扎胆总管后,其血清TNF鄄α和三酰甘油值相应增高,肝脏开始表达TGF鄄β1并逐日增多;解除梗阻后,又逐日减少直至正常。结论:细胞凋亡方式存在于阻塞性黄疸肝脏中,与胆红素、TNF鄄α、TGF鄄β1等密切相关。

Objective:To study the phenomenon of apoptosis in obstructive jaundice liver,and its molecular mechanism.Methods:After ligation of the common bile duct,apoptosis in the liver was observed by histology and in situ end labelling of fragmented DNA;and its changes were studied when internal drainage was instituted;meanwhile,the plasma TNF-α,bilirubin and triglyceride level was determined by ELISA and biochemical method,and the expression of TGF-β 1 by immunohistochemistry.Results:Three days after bile duct ligation,apoptosis in the liver rose markedly,and increased together with the bilirubin level;when internal biliary drainage was established,apoptosis started to decrease.Parallel to the appearance of apoptosis,the plasma TNF-α,triglyceride level and the amount of TGF-β 1 expression in liver rose too.Conclusions:Apoptosis as a mechanism of cell death exists in obstructive jaundice and is closely related to the level of bilirubin,TNF-αand TGF-β_1 expression.