目的 观察黄芪甲苷（astragaloside IV，AST IV）改善人肝癌HepG2细胞胰岛素抵抗作用，基于药效团模型相互匹配和分子对接预测和验证AST IV可能作用靶点，探讨AST IV改善胰岛素抵抗机制。方法 采用高浓度胰岛素诱导HepG2细胞制备胰岛素抵抗模型，AST IV干预后，检测细胞葡萄糖消耗量，基于药效团模型相互匹配和分子对接预测AST IV可能作用靶点，Western blotting法检测通路相关蛋白表达。结果AST IV干预能显著增加胰岛素抵抗的HepG2细胞葡萄糖消耗量，且效应与盐酸吡格列酮相当；基于药效团模型相互匹配和分子对接预测AST IV作用靶点与酪氨酸磷酸酶1B（PTP1B）相关；Western blotting结果显示，胰岛素抵抗的HepG2细胞PTP1B蛋白表达水平显著升高，而胰岛素信号通路关键蛋白磷酸化的胰岛素受体（p-IR）和磷酸化的胰岛素受体底物1（p-IRS-1）表达水平显著降低；AST IV的干预能显著降低PTP1B蛋白表达水平，升高p-IR和p-IRS-1蛋白表达水平。结论 AST IV能显著改善高浓度胰岛素诱导的HepG2细胞的胰岛素抵抗，其作用机制与抑制PTP1B激活胰岛素信号通路有关。

Objective To research the effects of astragaloside IV (AST IV) on improving insulin resistance in HepG2 cells, and predict and verify the AST IV possible targets based on pharmacophore model matching and molecular docking. Methods HepG2 cells insulin resistance model was induced with high concentration insulin. After being interfered by AST IV, the glucose consumption was characterized by glucose test, AST IV possible targets were predicted by pharmacophore model matching and molecular docking, the expressions of related pathway protein were detected by Western blotting. Results AST IV significantly increased the glucose consumption in insulin-resistant HepG2 cells, the possible target of AST IV may be related to tyrosine phosphotase 1B (PTP1B) based on pharmacophore model matching and molecular docking. The Western blotting results showed that, the level of PTP1B was significantly increased and the levels of p-IR and p-IRS-1 were significantly decreased in insulin-resistant HepG2 cells. The intervention of AST IV decreased the levels of PTP1B, and increased the levels of p-IR and p-IRS-1. Conclusion AST IV can significantly improve insulin resistance of insulin induced HepG2 cells, and its mechanism is related to inhibiting PTP1B and activating insulin signaling pathways.

国家自然科学基金资助项目（81503385）；湖南中医药大学“十三五”一级学科基础医学建设项目