吡格列酮保护乳鼠心肌细胞与ATP敏感性钾通道表达的关系

目的探讨吡格列酮对缺氧复氧诱导的乳鼠心肌细胞凋亡和心肌细胞ATP敏感性钾通道亚单位表达的影响。方法原代培养的sD乳鼠心肌细胞随机分为6组：溶媒组、缺氧复氧组、0．1μmol／L吡格列酮组、1．0μmol／L吡格列酮组、2．0μmol／L吡格列酮组、2．0μmol／L吡格列酮＋GW9662组（GW9662组），药物预处理24h后建立缺氧复氧模型，利用膜联蛋白-v与溴化丙啶双染法检测心肌细胞凋亡，利用RT—PCR及Western—blot技术检测心肌细胞ATP敏感性钾通道亚单位的表达。结果0．1、1．0、2．0μmol／L吡格列酮组心肌细胞凋亡率与缺氧复氧组及GW9662组比较差异有统计学意义（P〈0．05）；0．1、1．0、2．0μmol／L吡格列酮组心肌细胞线粒体ATP敏感性钾通道（mitoKATP）亚单位Kir6．1mRNA及蛋白的表达与缺氧复氧组及GW9662组比较差异有统计学意义（P〈0．05），各组细胞膜ATP敏感性钾通道（sarcKATP）亚单位Kir6．2mRNA表达间差异无统计学意义（P〉0．05）。结论吡格列酮抑制缺氧复氧诱导的乳鼠心肌细胞凋亡，此保护作用可能与激活PPARγ及上调mitoKATP通道亚单位表达有关，sarcKATP未参与这种保护过程。

Relationship of Pioglitazone Protecting Neonate Rat Cadiocyte to ATP-sensitive Potassium Channel Subunit Expression

Objective To investigate the effect of pioglitazone on hypoxia-reoxygenation-induced apoptosis in neonatal rat cardiac myocytes and on ATP-sensitive potassium channel subunit expression.Methods Primarily cultured SD neonatal rat cardiomyocytes were randomly divided into groups A(menstruum group),B (hypoxia-reoxygenation group),C (treated with 0.1 μmol/L pioglitazone),D (with 1 μmol/L),E (with 2 μmol/L),F (with 2 μmol/L pioglitazone+PPARγ specific antagonist GW9662).Hypoxia-reoxygenation models were established after 24 h of drug pre-treatment,and apoptoses of myocardial cells were detected by annexin-v and FITC/PI,and APT-sensitive potassium channel subunit expression by RT-PCR and Western-blot.Results Groups C,D,E were significantly different from groups B,F in myocardial apoptosis rate(P＜0.05),and in myocardial mitochondrial ATP-sensitive potassium channel (mitoKATP) subunit Kir6.1 mRNA and protein expressions(P＜0.05),but there was not difference in membrane ATP-sensitive potassium channel (sarcKATP) subunit Kir6.2 mRNA expressions between all groups(P＞0.05).Conclusion Pretreatment with pioglitazone can reduce hypoxia-reoxygenation-induced myocardial cells apoptosis in neonatal rats,which may related with activated PPARγ and up-regulated mitoKATP channel subunit expression,and in which sarcKATP dose not involved.