目的 通过网络药理学、分子对接及体内外实验研究脑心清对高脂饮食诱导的非酒精性脂肪肝 （Non-alcoholic fatty liver disease，NAFLD） 的治疗效果及作用机制。方法 选择 ApoE-/-小鼠给予高脂饮食 12 周，进行NAFLD 模型复制，继而使用脑心清干预 12 周后，进行生化学、组织病理学检测，主要包括血脂、肝功能、血清炎症因子及肝脏苏木素-伊红 （HE） 、油红 O、天狼星红染色，评估脑心清对高脂饮食诱导的 NAFLD 的疗效。通过网络药理学及分子对接技术预测脑心清的作用靶点。通过 HepG2 细胞蛋白质印迹 （Western Blot） 实验验证脑心清的作用机制。结果 血清生化学及肝脏组织病理学结果显示，脑心清可以明显改善高脂饮食诱导的肝脏脂质积聚、肝细胞损伤及炎症反应。网络药理学及分子对接分析结果表明，脑心清可能通过 AMP 依赖的蛋白激酶 （AMP-activated protein kinase，AMPK） /沉默调节蛋白 1 （Sirtuin 1，SIRT1） 通路影响脂质代谢。体外细胞实验证实脑心清的作用机制主要是激活 AMPK/SIRT1 通路，上调下游肉碱棕榈酰转移酶 1A（Carnitine palmitoyltransferase 1，CPT1A） 的表达，促进脂肪酸氧化，最终改善 NAFLD。结论 脑心清通过激活 AMPK/SIRT1 通路促进脂肪酸氧化改善 NAFLD。

Objective This study aims to investigate the therapeutic effect and mechanism of Naoxinqing on non-alcohol fatty liver disease （NAFLD） induced by a high-fat diet through network pharmacology，molecular docking and in vitro and in vivo experiments. Methods ApoE-/-mice were given a high-fat diet for 12 weeks to establish the NAFLD model，followed by a 12-week Naoxinqing administration. To evaluate the therapeutic effect of Naoxinqing on NAFLD induced by a high-fat diet，biochemical and histopathological experiments were performed，including assessment of blood lipids，liver function，serum inflammatory factors，as well as Hematoxylin and eosin（HE），Oil red O，and Sirius red staining of liver. Subsequently，network pharmacology and molecular docking techniques were employed to predict the key targets of Naoxinqing. Finally，the mechanism of Naoxinqing was validated by Western Blot in HepG2 cells and liver tissue. Results The results of serum biochemistry and liver tissue pathology showed that Naoxinqing can significantly improve high-fat diet-induced hepatic lipid accumulation，hepatocellular injury，and inflammation. Network pharmacology and molecular docking analysis results suggested that Naoxinqing may affect lipid metabolism through the AMP-activated protein kinase （AMPK）/Sirtuin 1 （SIRT1）pathway. Finally，in vitro cell experiment confirmed that the main mechanism of Naoxinqing is to activative the AMPK/SIRT1 pathway， upregulate the expression of downstream carnitine palmitoyltransferase 1 （CPT1A），promote fatty acid oxidation，and ultimately improve NAFLD. Conclusion This study demonstrated that Naoxinqing improved NAFLD by promoting fatty acid oxidation through the activation of the AMPK/SIRT1 pathway.

R285.5

广东省基础与应用基础研究基金项目 （2022A1515220067）；广州市科技局市属高校联合项目 （202201020257）；广州中医药大学交叉学科建设项目 （A1-2601-24-415-110Z78）。