吡格列酮预处理对大鼠缺血-再灌注心肌细胞凋亡及线粒体ATP敏感性钾通道的影响论文.docVIP

　　吡格列酮预处理对大鼠缺血/再灌注心肌细胞凋亡及线粒体ATP敏感性钾通道的影响论文 李健,冯义柏,田莉,郎明健,杨汉东 【摘要】 目的: 观察吡格列酮(Pio)对在体大鼠心肌缺血/再灌注心肌细胞凋亡及线粒体ATP敏感性钾通道影响，探讨Pio对心肌缺血损伤保护作用及其机制. 方法: 24只SD大鼠随机分为假手术组（SO组）,缺血/再灌注组（I/R组），Pio预处理组（Pio组）和线粒体ATP敏感性钾通道阻滞剂5羟基葵酸（5HD）+Pio组（5HD+Pio组）4组. 各组于缺血/再灌注前24 h尾静脉注射相应溶媒及药物，5HD+Pio组注入5HD 10 mg/kg 30 min后再给予Pio 3 mg/kg；Pio组只注入Pio 3 mg/kg；SO组不结扎前降支，4 h后取出心脏；余三组结扎前降支30 min，再灌注4 h后取出心脏. 用透射电镜观察心肌线粒体超微结构的改变；采用TUNEL法和免疫组化法检测缺血心肌细胞凋亡和Bcl2，Bax，Caspase3蛋白的表达以及RTPCR法测Fas mRNA的表达. 又另取18只SD大鼠随机分成SO.freelRNA的表达水平. I/R组与5HD+Pio组相比,差异无统计学意义(P 0.05). 结论：Pio预处理可通过保护心肌线粒体结构，减少心肌细胞凋亡及梗死范围,保护缺血心肌损伤作用可被线粒体ATP敏感性钾通道阻滞剂所对抗. 【关键词】 吡格列酮；缺血再灌注；凋亡；线粒体；钾通道 【Abstract】 AIM: To observe the effects of pioglitazone on myocardial apoptosis induced by myocardial ischemia/reperfusion (I/R) injury and mitochondria ATPsensitive potassium channel in rats in vivo and to explore the mechanism of pioglitazone protection from myocardial I/R injury. METHODS: Tly divided into 4 groups: shamoperated group, I/R group, pioglitazone treatment group and 5hydroxydecanoic acid (5HD)+pioglitazone group. Apart from the shamoperated group, I/R, pioglitazone and 5HD+pioglitazone groups inistered solvent or drugs intravenously 24 h before occlusion,.freelg/kg) and 5HD (10 mg/kg) plus pioglitazone (3 mg/kg). In 5HDpioglitazone group, 5HD in before pioglitazone injection. The shamoperated group in in I/R, pioglitazone and 5HD+pioglitazone groups. Then the left anterior descending branch oved to be used for observing the ultrastructure of mitochondria and measuring the apoptosis rate by TUNEL and detecting the expressions of Bcl2, Bax, Caspase3 proteins munohistochemistry and Fas mRNA ly divided into 3 groups: shamoperated group, I/R group, pioglitazone treatment group and the size of myocardial infarction age of mitochondrial ultrastructure in pioglitazone group operated group, the apoptosis and positive cell index (PCI) of Bcl2, Bax, Caspase3 proteins and the level of Fas mRNA in I/R, pioglitazone and 5