【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。更多还原

【Abstract】 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 adenosine monophosphate-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 ligation,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 PPARα and carnitine palmitoyl transferase-1(CPT-1)mRNA level by real-time fluorescent quantitation PCR,and total AMPKα protein,phosphorylation-AMPKα(p-AMPKα),PPARα and CPT-1 of myocardium by Western Blot.Results LVEDP and ±dp/dtmax reduced significantly(both P < 0.01),LVEDP increased significantly(P < 0.01),plasma FFA,myocardial FFA and triglyceride elevated significantly(both P < 0.01),PPARα,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/dtmax increased significantly(both P < 0.01),LVEDP decreased significantly(P < 0.01),plasma FFA,myocardial FFA and triglyceride decreased significantly(both P < 0.01),PPARα,CPT-1 mRNA and protein,and p-AMPKα protein level of myocardium increased significantly(all P < 0.01) in group MI-Ex as compared with group MI-Sed.Conclusion Long-term aerobic exercise upregulated expression of CPT-1,promoted FFA oxidative utilization through activation of AMPK-PPARα signal pathway in rats with chronic heart failure,and thus decreased the lipid accumulation and improved the cardiac function of the rats.更多还原