摘要
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(mi-toKATP)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。
Objective To investigate the effect of pioglitazone on hypoxia -reoxygenation -induced apoptosis in neonatal rat cardiac myoeytes and on ATP - sensitive potassium channel subunit expression. Methods Primarily cultured SD neo- natal rat eardiomyocytes were randomly divided into groups A （ menstruum group ）, B （ hypoxia - reoxygenation group ）, C （treated with 0. 1μmol/L pioglitazone）, D （with 1 μLmoL/L）, E （with 2 μmol/L）, F （with 2 μmo]/L piogiitazone ＋ 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 - reoxygcnation - induced myocardial cells apoptosis in neonatal rats, which may related with activated PPAR~/and up - regulated mitoKATP channel subunit expression, and in which sarcKATP dose not involved.
出处
《中国全科医学》
CAS
CSCD
北大核心
2010年第2期163-166,共4页
Chinese General Practice
基金
国家自然科学基金项目(30270551)
关键词
吡格列酮
肌细胞
心脏
缺氧复氧ATP敏感性钾通道
Pioglitazone
Myocytes, cardiac
Hypoxia/reoxygenation, ATP - sensitive potassium channel
