吡格列酮保护缺氧复氧诱导乳鼠心肌细胞凋亡的离子通道机制

目的观察吡格列酮对缺氧复氧大鼠心肌细胞凋亡的保护作用,并探讨保护作用与ATP敏感性钾通道开放的关系。方法原代培养的SD乳鼠心肌细胞,分为8组:溶媒组、缺氧复氧组、0.1μmol/L吡格列酮组、1 μmol/L吡格列酮组、2μmol/L吡格列酮组、2μmol/L吡格列酮+30μmol/L HMR-1098组、2μmol/L吡格列酮+0.5mmol/L 5-羟基葵酸盐(5-HD)组、2μmol/L吡格列酮+30μmol/L HMR-1098+0.5 mmol/L 5-HD组。利用膜联蛋白-V与碘化丙啶双染法及Hoechst 33258染色法检测心肌细胞凋亡。结果缺氧复氧组乳鼠心肌细胞发生明显凋亡,经吡格列酮预处理后减少心肌细胞凋亡(P<0.05);与0.1μmol/L、1μmol/L及2μmol/L吡格列酮组比较,5-HD削弱吡格列酮抑制心肌细胞凋亡的作用(P<0.05),HMR-1098无作用(P>0.05)。结论吡格列酮对缺氧复氧乳鼠心肌细胞凋亡具有保护作用,线粒体ATP敏感性钾通道的开放可能介导了吡格列酮的保护作用。

Ion channel mechanism of cardioprotection of pioglitazone against hypoxia-reoxygenation induced apoptosis

Objective To investigate the protective effect of pioglitazone against the hypoxia-reoxy-genation induced cardiac myocytes apoptosis and the role of ATP-sensitive potassium channel in the cardioprotection of pioglitazone. Methods Primary cultured cardiomyocytes of neonatal Sprague Dawley rats were divided into 8 groups: vehicle, hypoxia-reoxygenation,0.1 μmol/L pioglitazone, 1 μmol/L pioglitazone, 2 μmol/L pioglitazone, 2 μmol/L pioglitazone + HMR-1098, 2 μmol/L pioglitazone+5-hydroxy decanoate (5-HD), 2 μmol/L pioglitazone + HMR-1098+5-HD. The cells were stained with Annexin-V FITC/PI and Hoechst-33258 which was used to detect the apoptosis of cardiomyocytes. Results Apoptosis index in hypoxia-reoxygenation group significantly increased compared with the vehicle group (P<0.05). Pioglitazone decreased apoptosis index in dose-dependent manner. 5-HD attenuated the protective effect of 2.0μmol/L pioglitazone against apoptosis (P<0.05) and HMR-1098 had no effect on the protection. Conclusions Pretreatment with pioglitazone can reduce cardiomyocyte apoptosis induced by hypoxia-reoxygen-ation. Pioglitazone may exert cardioprotection against apoptosis via opening mitoK_(ATP) channel and not via sarcK_(ATP) channel.