免疫性肝损伤和酒精性肝损伤中CYP2E1代谢活力的差异性变化

The difference of metabolism activity of CYP2E1 between in immune liver damage rats and in alcohol-mediated hepatic injury rats

目的:观察免疫性肝损伤和酒精性肝损伤对大鼠CYP2E1代谢活力的影响。方法:采用尾静脉注射卡介苗诱发大鼠产生免疫性肝损伤,采用白酒灌胃法制备大鼠酒精性肝损伤模型,HPLC法测定经CYP2E1代谢的探针药物氯唑沙宗血药浓度经时变化。结果:卡介苗刺激可致大鼠肝脏明显肿大,大量单核、淋巴细胞浸润,肉芽肿形成;致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性减弱,AUC增大,Cmax增大。酒精性肝损伤可致肝小叶结构不清,肝索排列紊乱,肝细胞体积增大,呈弥漫性中度水变性,肝窦受压,大部分肝细胞胞浆内见大小不等的脂肪空泡。致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性增强,AUC减少,Cmax减少。结论:免疫性肝损伤可致CYP2E1代谢活性降低,酒精性肝损伤可致CYP2E1代谢活性增强。

OBJECTIVE To compare the difference of metabolism activity of CYP2E1 between in immune liver damage rats and in alcobol-mediated hepatic injury rats. METHODS Immune liver damage was induced by intravenous injection of Bacillus Calmette-Guerin vaccine, （BCG, 125 mg·kg^-1 for 2 weeks in vivo. Alcohol-mediated hepatic injury model was established by ig white wine. The enzyme CYP2E1 kinetics of the probes chlorzoxazone was evaluated by higkperformance liquid chromatography（HPLC）. The serum concentra tion of chlorzoxazone after single oral administration in rats reflects hepatic CYP2E1 catalyzing activity. RESULTS Rat liver became tumefaction obviously, and a lot of granuloma forming, inflammatory cells .soakage were observed in rat hepatic tissues after BCG injection for 2 weeks. Furthermore, CYP2E1 metabolism activity was also decreased By BCG-induced immune injury in rats. In contrast, the liver histopathology in ethanol-induced hepatic injury revealed milcl-to-moderate steatosis and mild necroinflammation, CYP2E1 metabolism activity was increased. CONCLUSION The CYP2E1 metabolism activity was decreased in immune liver damage rats,on the contrary, CYP2E1 metabolism activity was increased in alcohol-mediated hepatic injury rats.