目的 觀察黃芪甲苷（astragaloside IV，AST IV）改善人肝癌HepG2細胞胰島素抵抗作用，基于藥效團模型相互匹配和分子對接預測和驗證AST IV可能作用靶點，探討AST IV改善胰島素抵抗機制。方法 采用高濃度胰島素誘導HepG2細胞制備胰島素抵抗模型，AST IV干預后，檢測細胞葡萄糖消耗量，基于藥效團模型相互匹配和分子對接預測AST IV可能作用靶點，Western blotting法檢測通路相關蛋白表達。結果AST IV干預能顯著增加胰島素抵抗的HepG2細胞葡萄糖消耗量，且效應與鹽酸吡格列酮相當；基于藥效團模型相互匹配和分子對接預測AST IV作用靶點與酪氨酸磷酸酶1B（PTP1B）相關；Western blotting結果顯示，胰島素抵抗的HepG2細胞PTP1B蛋白表達水平顯著升高，而胰島素信號通路關鍵蛋白磷酸化的胰島素受體（p-IR）和磷酸化的胰島素受體底物1（p-IRS-1）表達水平顯著降低；AST IV的干預能顯著降低PTP1B蛋白表達水平，升高p-IR和p-IRS-1蛋白表達水平。結論 AST IV能顯著改善高濃度胰島素誘導的HepG2細胞的胰島素抵抗，其作用機制與抑制PTP1B激活胰島素信號通路有關。

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.

國家自然科學基金資助項目（81503385）；湖南中醫(yī)藥大學“十三五”一級學科基礎醫(yī)學建設項目