Astragaloside IV Regulates Expression of ATP-sensitive Potassium Channel Subunits after Ischemia-reperfusion in Rat Ventricular Cardiomyocytes

作     者：韩向晖 刘萍 章怡祎 张娜 陈富荣 蔡珏峰 

作者机构：Scientific Research Center Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Science and Technology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine 

出 版 物：《Journal of Traditional Chinese Medicine》 (中医杂志（英文版）)

年 卷 期：2011年第31卷第4期

页      面：321-326页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by Key Project of Shanghai Education Commission (No.07ZZ56) National Natural Science Foundation of China (No.30873340) National 11th-Five Year Research Program of China (No.2007BAI20B078) Program for Innovative Research Team in University of Shanghai Education Commission 

主　　题：Astragaloside IV pinacidil myocardial ischemia reperfusion KATP channels 

摘      要：Objective: Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the heart from myocardial ischemic injury, but the mechanisms of action are unknown. ATP-sensitive potassium (KATP) channels are activated during ischemia and exert a compensatory protective effect on cardiomyocytes. We therefore examined the effects of AsIV on KATP channel currents and channel expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion injury. Methods: Forty Wistar rats were divided into five groups: control group, ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group and IP + AsIV group. The ischemia-reperfusion injury model was established in enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The different drugs were applied for 10-15 min, and the KATP channel current (IKATP) was recorded with voltage-clamp mode by whole-cell patch-clamp technique. Protein and mRNA expression of the KATP channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR. Results: The KATP current in IP group was significantly greater than that in control group (211.45±33.67 vs 83.51±23.67 pA; P0.01). Glibenclamide (10 μmol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known channel opener pinacidil (50 μmol/L) significantly increased IKATP (P0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P0.01 vs IP group). Conclusion: The protective effects of AsIV in ischemia-reperfusion injury may be related to the up-regulation of several KATP channel subunits and facilitation of KATP currents.