有氧运动抑制心力衰竭大鼠心脏脂质沉积:AMPK-PPARα信号通路的作用  

Aerobic Exercise Lessens Myocardial Excessive Lipid Accumulation and Improves the Cardiac Function of Rats with Chronic Heart Failure:Role of AMPK-PPARα Signal Pathway

作　　者：赛庆彬[1] 马延超[2] 朱荣[3] 

机构地区：[1]曲阜师范大学体科院,山东曲阜273165 [2]洛阳师范学院 [3]温州医学院

出　　处：《中国运动医学杂志》2012年第12期1081-1086,1108,共7页Chinese Journal of Sports Medicine

基　　金：河南省科技厅项目(122300410257)

摘　　要：目的:观察8周有氧运动对心力衰竭大鼠心脏脂质沉积和心功能的影响,探讨AMP激活的蛋白激酶(AMPK)—过氧化物酶体增殖物激活受体α(PPARα)信号通路在其中的作用机制。方法:结扎大鼠冠状动脉建立心梗后心衰模型,术后4周随机分为假手术安静组(Sham组)、心梗安静组(MI-Sed组)和心梗运动组(MI-Ex组)。MI-Ex组进行为期8周的跑台运动,Sham组和MI-Sed组保持安静状态。实验结束后,左心室导管法测定血流动力学参数包括左心室收缩期压力(LVSP)、左心室舒张末期压力(LVEDP)、左心室压力最大上升速率(+dp/dtmax)和左室压力最大下降速率(-dp/dtmax);比色法测定心肌和血浆游离脂肪酸(FFA)水平;氧化酶法测定心肌甘油三酯含量;实时荧光定量PCR检测心肌PPARα和肉碱棕榈酰转移酶-1(CPT-1)mRNA水平;Western blot法检测心肌总AMPKα、磷酸化的AMPKα(p-AMPKα)、PPARα和CPT-1蛋白表达水平。结果:与Sham组比较,MI-Sed组LVSP、±dp/dtmax显著性下降(均为P<0.01),LVEDP则显著性升高(P<0.01);血浆FFA、心肌FFA和甘油三酯水平升高(均为P<0.01);心肌PPARα和CPT-1 mRNA及蛋白显著降低(均为P<0.01),p-AMPKα蛋白显著升高(P<0.05)。与MI-Sed组比较,MI-Ex组LVSP、±dp/dtmax显著性升高(均为P<0.01),LVEDP则显著性下降(P<0.01);血浆FFA、心肌FFA和甘油三酯水平显著降低(均为P<0.01);心肌PPARα和CPT-1 mRNA和蛋白以及p-AMPKα蛋白水平均显著性升高(均为P<0.01)。结论:长期有氧运动活化AMPK-PPARα信号通路,上调CPT-1表达,促进心肌对FFA的氧化利用,从而减轻HF后心脏脂质过度沉积、改善脂毒性心脏异常并提高心功能。Objective To observe the effects of 8-week aerobic exercise on lipid accumulation,heart function and exercise tolerance in rat with chronic heart failure and to investigate the role of adenosinemonophosphate-activated protein kinase （AMPK）-peroxisome proliferator-activated receptor α （PPARα） signal pathway. Methods Heart failure model was established by ligating anterior descending branch of coronary artery of rats. 4 weeks after the hgation,the animals with myocardial infarction （MI） were randomly divided into：sedentary MI group （MI-Sed） and MI plus exercise group （MI-Ex）. A sham operation group （Sham） was used as control. Rats in group MI-Ex performed an 8-week treadmill exercise while in groups Sham and MI-Sed stayed sedentary. After experiment,left ventricular systolic pressure （LVSP）,left ventricular end-diastolic pressure （LVEDP）,maximal developing rate of left ventricular pressure（＋dp/dtmax） and maximal descending rate of left ventricular pressure（-dp/dtmax） were measured through ventricular catheter,myocardial and plasma free fat acid （FFA） by colorimetric method, myocardial triglyceride by oxidizing enzyme method, myocardial PPARot and carnitine palmitoyl transferase-1 （CPT-1）mRNA level by real-time fluorescent quantitation PCR ,and total AMPKct protein, phosph.grylation-AMPKα （p-AMPKα）,PPARα and CPT-1 of myocardium by Western Blot. Results LVEDP and ＋dp/dtm reduced significantly （both P 〈 0.01 ）,LVEDP increased significantly （P 〈 0.01 ）, plasma FFA,myocardial FFA and triglyceride elevated significantly （both P 〈 0.01）,PPARot,CPT-1 mRNA and protein decreased significantly（both P 〈 0.01 ） and p-AMPKα protein increased significantly （P 〈 0.05）in group MI-Sed as compared with group Sham. LVEDP and ±dp/dtmmax increased significantly （both P 〈 0.01）,LVEDP decreased significantly （P 〈 0.01）,plasma FFA,myocardial FFA and triglyceride decreased significantly （both P 〈 0.01 ）protein level of myocardium

关 键 词：有氧运动 心力衰竭 脂质沉积 AMP激活的蛋白激酶 过氧化物酶体增殖物激活受体 α 肉碱棕榈酰转移酶-1 

分 类 号：G804.2[文化科学—运动人体科学] R541.6[文化科学—体育学]