目的 探讨同仁乌鸡白凤丸（WJBF）对酒精性肝病的治疗作用及作用机制。方法 雌性C57BL/6N小鼠随机分为6组：对照组、模型组、水飞蓟素(阳性药，63 mg·kg^-1)组和WJBF高、中、低剂量(5.40、2.70、1.35 g·kg^-1)组，除对照组外，其余组采用Lieber-DeCarli液体饲料复制酒精性肝病小鼠模型。观察WJBF对模型小鼠体质量、肝脏指数和肝脏病理改变的影响；试剂盒法测定血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）指标的含量；取小鼠肝脏组织并测定肝脏组织中TC、TG、超氧化物歧化酶（SOD）、丙二醛（MDA）、乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）以及8-羟基脱氧鸟苷（8-OHdG）水平；用Western blotting法测定肝脏组织中细胞色素P4502E1（CYP2E1）、沉寂信息调节因子（SIRT1）和过氧化物酶增殖激活受体-γ共激活子-1α（PGC-1α）蛋白表达水平。结果 与模型组相比，WJBF中剂量能明显减缓模型小鼠体质量降低（P<0.01）;WJBF中、低剂量能明显降低模型小鼠肝脏指数（P<0.05、0.01）;WJBF高、中、低剂量能明显降低模型小鼠血清ALT和AST活性（P<0.05、0.01）;WJBF高、中、低剂量能明显降低血清和肝脏组织中TG水平（P<0.01）;WJBF能明显改善模型小鼠肝脏组织病理学变化；WJBF高、中、低剂量能明显升高模型小鼠肝脏组织中ADH和ALDH的活性（P<0.05、0.01）;WJBF中、低剂量能明显升高模型小鼠肝脏组织内SOD活性（P<0.05）;WJBF高、中、低剂量能明显降模型小鼠肝脏组织中MDA水平（P<0.01）;WJBF高、中、低剂量能明显降低肝脏组织中8-OHdG水平（P<0.01）;WJBF高、中、低剂量能明显降低模型小鼠肝脏组织中代谢酶CYP2E1表达水平（P<0.05、0.01）;WJBF高剂量能明显升高模型小鼠肝脏组织中SIRT1蛋白表达水平（P<0.05）;WJBF高、中、低剂量能明显升高模型小鼠肝脏组织中PGC-1α蛋白表达水平（P<0.01）。结论 WJBF对酒精性肝病有较好的治疗作用，其作用机制与药物加快酒精在体内代谢、抑制肝组织中代谢酶CYP2E1、激活SIRT1/PGC-1α信号通路有关。

Objective To explore the therapeutic effects and mechanisms of Tongren Wuji Baifeng Pill（WJBF） on alcoholic liver disease. Methods Female C57 BL/6N mice were randomly divided into six groups: control group, model group, silymarin(63 mg·kg^-1) group, and WJBF high, medium, and low dose(5.40, 2.70, 1.35 g·kg^-1) groups. Except for the control group, the other groups were treated with Lieber DeCarli liquid feed to replicate the alcoholic liver disease mouse model. The effects of WJBF on body weight, liver coefficient, and histopathological changes in the liver were observed. Serum levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, triglycerides（TG）, and total cholesterol（TC） were measured; Liver tissues were collected to determine levels of TC, TG, superoxide dismutase（SOD）, malondialdehyde（MDA）, ethanol dehydrogenase（ADH）, aldehyde dehydrogenase（ALDH） and 8-hydroxydeoxyguanosine（8-OHdG）; Western blotting was used to determine the protein expression levels of cytochrome P4502E1（CYP2E1）, silencing information regulatory factor（SIRT1）, and peroxisome proliferator activated receptor-γ co-activator-1α（PGC-1α） in liver tissue. Results Compared with the model group, the medium dose of WJBF significantly slowed down the reduction in body weight（P ＜ 0.01）; Both medium and low doses significantly reduced the liver coefficient（P ＜ 0.05, and 0.01）; All doses significantly decreased serum ALT and AST activity（P ＜ 0.05, and 0.01）; All doses significantly lowered serum and liver tissue TG levels（P ＜ 0.01）; WJBF significantly improved histopathological changes in liver tissues; All doses significantly increased ADH and ALDH activity in liver tissues（P ＜ 0.05, and 0.01）; Medium and low doses significantly increased SOD activity in liver tissues（P ＜ 0.05）; All doses significantly decreased MDA levels in liver tissues（P ＜ 0.01）; All doses significantly reduced 8-OHdG levels in liver tissues（P ＜ 0.01）; All doses significantly decreased CYP2E1 expression in liver tissues（P ＜ 0.05, and 0.01）; The high dose significantly increased SIRT1 protein expression in liver tissues（P ＜ 0.05）; All doses significantly increased PGC-1α protein expression in liver tissues（P ＜ 0.01）. Conclusion WJBF has good therapeutic effects on alcoholic liver disease, which may be related to its ability to accelerate alcohol metabolism, inhibit metabolic enzyme CYP2E1 in liver tissue, and activate the SIRT1/PGC-1α signaling pathway.

R285.5

北京市科技计划资助项目(Z241100009024041)