运动促进慢性心衰大鼠心肌线粒体生物合成与心肌重构  

Exercise Enhances Mitochondrial Biogenesis and Cardiac Remodeling in Rats with Heart Failure Induced by Myocardial Infarction

作　　者：刘涛[1,2] 张敏[1] 徐栋[1] 刘树森[3,1] 吉力立[4] 张勇[1] 

机构地区：[1]天津市运动生理与运动医学重点实验室,天津体育学院健康与运动科学系,天津300381 [2]集美大学体育学院 [3]中国科学院动物研究所生物膜与膜生物工程国家重点实验室 [4]美国威斯康辛大学麦迪逊分校运动学系

出　　处：《中国运动医学杂志》2011年第3期250-256,281,共8页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金(30470837);天津市社会发展重大科技攻关项目(05YFGDSF02100)共同资助

摘　　要：目的:观察心衰及心衰后进行有氧运动对大鼠心肌线粒体生物力能学、线粒体生物合成以及心功能的影响,探讨心衰的运动康复过程中的心肌线粒体适应机制。方法:雄性Wistar大鼠,心梗组(16只)开胸后结扎左冠状动脉前降支,造成心梗模型,假手术组(16只)开胸但不结扎冠状动脉,其余处理与心梗组相同。术后4周,心梗组和假手术组再随机分为心梗安静组(MI)、心梗运动组(MI+E)和假手术安静组(Sham)、假手术运动组(Sham+E),每组8只。运动组进行跑台训练,运动强度14米/分钟,每天40分钟,每周训练5天,共训练8周。术后12周,超声心动图检查各组大鼠心率(HR),心室收缩末期内径(LVIDs),舒张末期内径(LVIDd)和心功能指标射血分数(EF),缩短分数(FS),每搏输出量(SV),心输出量(CO)。提取心肌线粒体测定态3、态4呼吸和呼吸控制比(RCR),ATP生成活力。Western blot检查心肌线粒体生物合成调控因子PGC-1α,线粒体蛋白COXⅣ、COXⅠ蛋白表达。透射电镜观察各组心肌线粒体形态数量。结果:术后12周,假手术运动组LVIDs、LVIDd、EF、FS、SV、CO与假手术安静组比较无明显变化,态3呼吸、RCR、ATP生成活力高于假手术安静组,PGC-1α、COXⅣ、COXⅠ蛋白表达无明显变化。心梗安静组与假手术安静组比较,LVIDs、LVIDd增加,EF、FS、CO降低,SV无明显差异,态4呼吸增加,RCR、ATP生成活力降低,PGC-1α、COXⅣ、COXⅠ蛋白表达增加。心梗运动组与心梗安静组比较LVIDs、LVIDd增加,EF、FS降低,CO增加,HR增加,SV无明显差异,态3呼吸、RCR、ATP生成活力增加,PGC-1α、COX IV、COX I蛋白表达增加。结论:(1)心衰后心肌线粒体生物合成增加,可能是对心衰后心肌线粒体功能下降的一种代偿性反应。(2)心衰后进行运动训练能促进心肌线粒体生物合成,但线粒体生物合成增加并不能代偿心衰后心功能的下降,并有可能加重心肌重构。Objective The purpose of the present study was to investigate the influence of exercise on the cardiac mitochondrial function,mitochondrial biosynthesis and cardiac function in rats with heart failure induced by myocardial infarction（MI）.Methods Myocardial infarction was induced by ligating anterior descending branch of coronary artery of rats.Animals were divided into 4 groups： sham operation sedentary（Sham）,sham operation plus exercise（Sham＋E）,sedentary MI（MI）,and MI plus exercise（MI＋E）.4 weeks after the surgery,rats in Sham＋E and MI＋E groups ran on a treadmill（zero grade,14m/min,40min/day,5 days/week）for a total of 8 weeks while sedentary groups retained their own daily activity.Cardiac function and structure were measured using echocardiography.Mitochondrial respiratory rates of state 3 and state 4 were measured using a Clark-oxygen electrode,and respiratory control ratios（RCR）were determined.Marker of mitochondrial biosynthesis,PGC-1α,COXⅠ and COX Ⅳ were measured using Western blot.Ultrastructure of cardiac muscle and mitochondria were observed with electronmicroscopy.Results Sham＋E group had higher RCR,respiratory rate of state 3 and ATP synthesis rate than the Sham group,whereas there are no significant differences in PGC-1α,COXⅠ and COX Ⅳ protein expressions,and ventricular structure and cardiac function between the two groups.There are higher LVIDs and LVIDd,lower EF,FS and CO,higher state 4 respiratory rate,lowered RCR and ATP synthesis rate,and enhanced PGC-1α,COXⅠ,COX Ⅳ protein expressions in MI group as compared with that in sedentary Sham group.Compared to the sedentary MI group,MI＋E group had higher LVIDs and LVIDd,higher CO and HR,increased state 3 respiratory rate and RCR,and enhanced PGC-1α,COXⅠ and COX Ⅳ protein expressions,and mitochondria proliferation.Conclusions We concluded that（1）Mitochondrial dysfunction in the failing heart may cause mitochondrial biosynthesis.（2）Exercise can promote cardiac remodeling through enhanci

关 键 词：心衰 有氧运动 线粒体生物力能学 线粒体生物合成 

分 类 号：R873[医药卫生—运动医学]