吡格列酮对缺血-再灌注大鼠心肌梗死面积和线粒体ATP敏感性钾通道的影响  

The effects of preconditioning with pioglitazone on infarct size and nfitochondrial ATP-sensitive potassium channel in rats with ischemia-reperfusion

作　　者：李健[1] 安毅[1] 毛晓波[2] 曾秋棠[2] 徐庆科[1] 李丹[1] 

机构地区：[1]青岛大学医学院附属医院心血管内科,山东省青岛266000 [2]华中科技大学同济医学院附属协和医院心内科

出　　处：《中华急诊医学杂志》2009年第5期483-487,共5页Chinese Journal of Emergency Medicine

基　　金：湖北省“十一五”重大科技攻关项目（2006AA301A04）

摘　　要：目的观察PPAR7激动剂吡格列酮对在体大鼠心肌缺血-再灌注心肌梗死面积、缺血面积及线粒体ATP敏感性钾通道（mitoKArrP）影响，探讨其可能机制。方法健康雄性SD大鼠54只，分为实验一和实验二完成。在实验一中24只大鼠随机分4组，每组6只：（1）假手术对照组（SO）行冠脉穿线但小结扎，4h后取出心脏；（2）单纯I／R组于I／R前24h由尾静脉注入0．9％生理盐水，开胸结扎冠脉前降支30min，松解后再灌注4h；（3）5-HD＋吡格列酮组（5-HD＋Pio）于I／R前24h由尾静脉缓慢注入mitoKa口阻滞剂5羟基葵酸（10mg／kg），30min后再缓慢注入吡格列酮（3mg／kg），持续5min，24h后处理同I／R组；（4）吡格列酮预处理组（Ho）于缺血一再灌注前24h只注入吡格列酮（3mg／kg），持续5nlin，余处理同（3）。后三组结扎前降支30min、再灌注4h后取出心脏。Western blot法测P38MAPK、JNK和NFkBP65蛋白水平的表达。在实验二中SD大鼠30只，分为SO组、I／R组、Pio组、5-HD＋Pio组及单纯5-HD组（于I／R前24h由尾静脉缓慢注入5羟基葵酸10mg／kg，余同I／R组），再灌注4h后，测心肌缺血及梗死范围。多组间比较采用单因素方差分析（SNK-q检验），采用SPSS11．0软件系统分析，P〈0．05为差异具有统计学意义。结果（1）与I／R组（34．93±5．55）％相比，Pio组梗死面积（20．24±3．93％）明显减少（P〈0．05），5-HD＋Pio组和5-HD与I／R组相比差异无统计学意义（P〉0．05）；除SO组外，其他各组间心肌缺血面积差异无统计学意义（P〉0．05）。与SO组相比，I／R组P38MAPKmRNA、JNKmRNA及P38MAPK、JNK1、JNK2和NFxBP65蛋白表达水平明显增加（P〈0．05）；与I／R组相比Pio组能抑制以上水平的过度表达（P〈0．05）。结论吡格列酮预处理可通过减少心肌梗多匕范围起到抗缺血-再灌注损伤作用，该保护作用可能与开放线粒体ATP敏�Objective To observe the effects of preconditioning with pioglitazone on infarct size and mito- chondrial ATP-sensitive potassium channel in rats with ischemia-reperfusion, and to explore its possible mecha- nism. Method The whole experiment was divided into experiment I and II. In experiment I, 24 rats were ran- domly divided into four groups （6 rats in each group） ： （1）Shanl-operated （SO） group： the coronary artery of rat was threading without ligation, and the heart was removed by cutting immediately 4 hours later; （2） Ischemia- reperfusion （I/R） group： the rats were administered with 0.9% saline intravenously via caudal vein at 24 hours before ligating the left anterior descending branch of coronary artery for 30 minutes, and followed by reperfusion for 4 hours; （3）5-hydroxydecanoate plus pioglitazone（5HD ＋ Pio） group： the rats were injected with 10 mg/kg 5-hy- droxydecanoate （the blocker of mitocbondrial ATP-sensitive potassium channels, ） at 24 hottrs before ligation, and 30 minutes later, 3 mg/kg pioglitazone was given in 5 minutes, and then the rats were subjected to ischemia for 30 minutes, followed by reperfusion for 4 hours; （4）pioglitazone treatment group （Pio） ： the rats were given 3 mg/kg pioglitazone at 24 hours before occlusion, and then they were treated as done in the 5HD ＋ Pio group. In I/R, 5HD ＋ Pio and Pio group, the hearts were removed by cutting after reperfusion. Western blotting was used to detect the protein expression of P38MAPK, JNK and NFscB 1365. In experiment Ⅱ, 30 rats were randondy divided into five groups： SO, I/R, Pio, 5HD＋ Pio and 5-HD group （rats were treated as done in the rats of I/R group and were injected with 10 mg/kg 5-hydroxydeeanoate 24 h before isehemia/repeffusion）, and the size of myocardial in- farction and isehemia were measured after repeffusion. Statistical analyses were performed using SPSS10.0 soft- ware. Multiple comparisons were analyzed by one-way analysis of variance （SNK- q test）. P �

关 键 词：吡格列酮 心肌梗死面积 线粒体ATP敏感性钾通道 P38MAPK JNK NhB P65 

分 类 号：R542.22[医药卫生—心血管疾病]