目的 探讨Bcl-2家族蛋白在TNFα致肝损伤及肝细胞凋亡中的作用。方法 以TNFα联合D-氨基半乳糖诱发小鼠肝损伤，以免疫组织化学法检测Bax、Bak蛋白在鼠肝组织中的表达情况；并以Bcl-2腺病毒载体感染肝细胞，观察其抗肝细胞凋亡作用。结果 TNFα可引起严重的肝损伤并有广泛的肝细胞凋亡，伴Bax、Bak蛋白在肝细胞中表达增强；Bcl-2腺病毒感染可使肝损伤小鼠ALT水平由（1372.9±251.4）U/L下降至（796.5±78.7）U/L，统计分析差异有显著意义（P＜0.0005）。结论 TNFα诱导肝细胞凋亡可能与其诱导Bax、Bak蛋白在肝细胞中表达增强有关；Bcl-2腺病毒载体可在小鼠肝细胞中持续表达至少一个月并可部分抵抗TNFα诱发的肝细胞凋亡。%Objective To evaluate the role of Bcl-2 family proteins in hepatic apoptosis caused by TNF α and D-galactosamine. Methods We induced mouse liver injury with TNF α and D-galactosamine, and detected hepatic apoptosis, the expression of Bcl-2, Bax, and Bak proteins on hepatocytes by using TUNEL or immunohistochemistry, respectively. We also observed the expression of Bcl-2 protein on hepatocytes infected with Bcl-2 adenovirus vector and its protection against hepatocyte apoptosis. Results Hepatocyte apoptosis was induced in BalB/c mice pretreated with TNF α plus D-galactosamine, accompanying the enhanced expression of Bax, Bak proteins in hepatocytes. Bcl-2 protein was expressed in murine hepatocytes and lasted at least 1 month after injection of Bcl-2 adenovirus vector, which also lowered ALT level from 1372.9±251.4 U/L to 796.5±78.7 U/L and reduced hepatocyte apoptosis caused by TNF α and D-galactosamine. Conclusion The enhanced expression of Bax, Bak proteins may play a role in hepatocyte apoptosis induced by TNF α and D-galactosamine. D-galactosamine adenovirus vector can partially reduced hepatocyte apoptosis induced by TNF α and D-galactosamine.
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