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; P<0.01). 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 (P<0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P<0.01 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.
血清总胆固醇（total cholesterol,TC）、三酰甘油（triglyceride,TG）和低密度脂蛋白胆固醇（low density lipoprotein-cholesterol,LDL-C）水平增高及高密度脂蛋白胆固醇（high density lipoprotein-cholesterol,HDL-C）水平降低是动脉粥样硬化发生、发展的主要脂类危险因素,又是诱发冠心病的危险因素.
