慢性肝病肝细胞凋亡Fas、FasL、Bax、Bcl-2、Bcl-X_L、Bcl-2α等蛋白表达

Study on pathway of apoptosis in chronic liver disease

目的 探讨慢性肝病时肝细胞凋亡蛋白Fas、FasL、Bax、Bcl 2、Bcl XL、Bcl 2α等的表达与线粒体的改变。方法 慢性肝炎 72例、肝炎后肝硬化 2 9例 ,以上患者肝组织采用免疫组化SP法检测促凋亡蛋白Fas、FasL、Bax和抑凋亡蛋白Bcl 2、Bcl XL、Bcl 2α等的表达 ,并对其中 15例肝组织着重观察了线粒体的超微结构。结果 促凋亡蛋白与抑凋亡蛋白相比 ,表达差异有非常显著性 (P <0 .0 0 1) ,前者最高达 94.4%,明显高于后者的最高值 6 1.1%,两组Fas、FasL的表达程度以 ( +)、( ++)为主 ,未见差别 ;但慢性肝炎组Bax( +++)表达多达 16例 ( 2 2 .2 %)、肝硬化组未见 ( +++)表达者。提示慢性肝炎组有明显的细胞凋亡现象而肝硬化组的凋亡相对不活跃。凋亡肝细胞的线粒体普遍存在明显的改变 ,包括线粒体嵴的扩张 ,外膜破裂、基质外漏等。结论 慢性肝炎时肝细胞的凋亡激活途径很可能偏重以线粒体途径为主 ,但尚需进一步研究证实。

Objective To study the pathway of apoptosis occurred in chronic liver diseases. Methods Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post-hepatitis cirrhosis were studied. The appoptosis related proteins, including Fas、FasL、Bax、Bcl-2、Bcl-X L and Bcl-2α were examined immunohistochemically by SP method. Ultrastructures of liver cells from 15 cases with apoptosis were studied with attention to the mitochondrial changes. Results In the chronic hepatitis group, the positive rates of expression of Fas、FasL、Bax were higher than in Bcl-2、Bcl-X L 、Bcl-2α with statistical significance (P< 0.001). The intensity of expression of Fas、FasL was found generally at the grade of (+) or (++). In the cirrhosis group there were no expression of Bax of (+++) grade. While in the chronic hepatitis group 22.2%(15 cases ) was found Bax of (+++) grade. The proapoptotic protien Bax were signigicantly higher than in the cirrhosis group. It indicated the excessive apoptosis in the chronic hepatitis patients and comparatively quiescent state of apoptosis in cirrhosis group. Conspicuous changes of mitochondrial were found including dilation of cristae, outer membrane repture and leakage of the mitochondriad matrix. Conclusions The apoptosis of hepotocytes occurred in chronic hepatitis may be activated majorly through the mitochondrial pathway.