目的 探讨五味子醇甲通过调控B淋巴细胞瘤-2（Bcl-2）/Bcl-2相关X蛋白（Bax）/半胱氨酸蛋白酶-3（Caspase-3）信号通路预防酒精性肝损伤的作用机制。方法 将55只SPF级雄性C57BL/6J小鼠随机分为对照组、模型组、水飞蓟宾组及五味子醇甲10、30 mg/kg组，每组11只。各给药组于乙醇ig前给予相应药物进行预防性干预；除对照组外，其余各组均按10 mL/kg ig给予50%乙醇，每日1次，连续7 d，建立急性酒精诱导性肝损伤模型。检测各组小鼠肝脏指数、血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）活性及炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平；苏木精-伊红（HE）染色观察肝组织病理形态；dUTP缺口末端标记法（TUNEL）检测肝细胞凋亡情况；免疫组织化学法及蛋白免疫印迹法检测肝组织中Bcl-2、Bax和Caspase-3蛋白表达。结果 五味子醇甲10、30 mg/kg组及水飞蓟宾组均能降低肝脏指数，血清AST、ALT活性及IL-1β、TNF-α、IL-6炎症因子水平（P＜0.05），减轻肝细胞肿胀、胞质疏松及空泡样改变等病理损伤，减少TUNEL阳性凋亡细胞数量，且五味子醇甲30 mg/kg组改善趋势更明显；免疫组织化学及蛋白免疫印迹法结果显示，五味子醇甲干预后Bcl-2蛋白表达升高，Bax、Caspase-3蛋白表达降低（P＜0.05）。结论 五味子醇甲预防性改善酒精性肝损伤的作用机制可能与调控Bcl-2/Bax/Caspase-3信号通路，抑制肝细胞凋亡和减轻炎症反应有关。

Objective To investigate the mechanism by which schisandrol A prophylactically ameliorates alcoholic liver injury via the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax)/cysteine protease-3 (Caspase-3) signaling pathway. Methods Fifty-five SPF-grade male C57BL/6J mice were randomly divided into control group, model group, silibinin group, schisandrol A 10, 30 mg/kg group, with 11 mice in each group. The administration groups received the corresponding drug for preventive intervention before ethanol gavage. Except for the control group, mice in the other groups were intragastrically administered 50% ethanol at a dose of 10 mL/kg once daily for 7 consecutive days to establish an acute ethanol-induced liver injury model. The liver index, serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected. Hematoxylin-eosin (HE) staining was performed to observe the pathological morphology of liver tissues. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect hepatocyte apoptosis. Immunohistochemistry and Western blot were adopted to determine the protein expressions of Bcl-2, Bax and Caspase-3 in liver tissues. Results Compared with the model group, the silybin group and schisandrol A 10, 30 mg/kg groups significantly reduced the liver index, serum AST and ALT activities, and the levels of IL-1β, TNF-α and IL-6 (P < 0.05), alleviated pathological injuries such as hepatocellular swelling, cytoplasmic rarefaction and vacuolar degeneration, and decreased the number of TUNEL-positive apoptotic cells, with more prominent ameliorative effects observed in the schisandrol A 30 mg/kg group. The results of immunohistochemistry and Western blot revealed that schisandrol A intervention up-regulated the protein expression of Bcl-2 and down-regulated the protein expressions of Bax and Caspase-3 (P < 0.05). Conclusion The preventive protective effect of schisandrol A against alcoholic liver injury may be associated with regulating the Bcl-2/Bax/Caspase-3 signaling pathway, inhibiting hepatocyte apoptosis and mitigating inflammatory response.

R286.5

陕西省自然科学基金资助项目（2023-JC-YB-69B）；陕西省科技厅自然基础研究计划项目（2025JC-YEMS-951）；秦创原中医药产业创新聚集区项目（L2024-QCY-ZYYJJQ-X139，L2024-QCY-ZYYJJQ-X129）；博士科研启动金（306/17102032233）；陕西中医药大学研究生教育教学改革创新项目（JGCX202404）；自然科学基础研究计划一般项目面上项目（2026JC-YBMS-0984）