长期有氧运动对慢性心力衰竭大鼠心肌能量代谢的调节

摘要

为探讨长期有氧运动对慢性心力衰竭大鼠心肌能量代谢的调节及可能机制.将结扎大鼠冠状动脉建立心梗后心衰模型,休息4周后随机分为假手术安静组(Sham)、心梗安静组(MI-Sed)和心梗运动组(MI-Ex),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/dt)max)和左室压力最大下降速率((-dp/dt)max)；Masson 染色进行心脏组织病理学观察；比色法测定心肌糖原、脂肪酸(FA)和乳酸含量；实时荧光定量PCR检测心肌过氧化物酶体增殖物激活受体α(PPARα)和肉碱棕榈酰转移酶-1(CPT-1)mRNA水平；Western blot法检测心肌AMPK、葡萄糖转运蛋白4(GLUT4)和过氧化物酶体增殖物受体γ共激活因子-lα(PGC-1α)表达水平.结果得到,与Sham组比较,MI-Sed组LVSP、±(dp/dt)max都非常显著性下降(P<0.01),LVEDP则都非常显著性升高(P<0.01)；心肌糖原含量降低(P<0.01)、FA与乳酸含量升高(均为P<0.01)；心肌PPARα和CPT-1 mRNA降低(P<0.01),磷酸化AMPKα(p-AMPKα)蛋白水平升高(P<0.05)、GLUT4和PGC-1α蛋白下降(P<0.01).与MI-Sed组比较,MI-Ex组LVSP、±(dp/dt)max都非常显著性升高(P<0.01),LVEDP则非常显著性下降(P<0.01)；心肌糖原含量升高(P<0.05),FA 和乳酸含量下降(P<0.01)；心肌 PPARα和 CPT-1 mRNA 以及p-AMPKα、GLUT4和PGC-1α蛋白水平均非常显著性升高(P<0.01).结果表明,长期有氧运动通过激活AMPK及其下游信号通路改善了HF心脏的代谢性重塑并提高心功能.%In order to probe into regulation made by long-term aerobic exercising on the myocardial energy metabo-lism of rats suffering a chronic heart failure and any possible mechanism, the authors established a post myocardial infarction heart failure model after having ligated the coronary artery of the rats, let the rats rest for 4 weeks, then divided them randomly into a sham operation sedentary group (Sham), a myocardial infarction sedentary group (MI-Sed) and a myocardial infarction exercising group (MI-Ex). The rats in the MI-Ex group exercised on a tread-mill for 8 weeks, while the rats in the Sham and MI-Sed groups maintained a sedentary condition. After the experi-ment was completed, by using the left ventricle tube method the authors measured hemodynamic parameters, which include left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal devel-oping rate of left ventricular pressure (+(dp/dt)max) and maximal descending rate of left ventricular pressure (-(dp/dt)max);by means of Masson dyeing the authors carried out histopathological observation;by using the colorimetric method the authors measured myocardial glycogen, fat acid (FA) and lactic acid content;by using real-time fluorescent quantitation PCR the authors determined myocardial peroxisome proliferator-activated receptor α (PPARα) and car-nitine palmitoyl transferase-1 (CPT-1) mRNA level;by using the Western blot method, the authors measured AMPK, glucose transporter (GLUT4), peroxisome proliferator-activated receptorγcoactivator lα(PGC-1α) protein of myocar-dium. The authors revealed the following findings: as compared with the rats in the Sham group, the LVSP and ±(dp/dt)max of the rats in the MI-Sed group decreased significantly (P<0.01), their LVEDP increased significantly (P<0.01);their myocardial glycogen content decreased (P<0.01), their FA and lactic acid content increased (P<0.01);their PPARα, CPT-1 mRNA decreased (P<0.01); their phosphorylated AMPKα (p-AMPKα) protein level increased (P<0.05), their GLUT4 and PGC-1αdecreased (P<0.01);as compared with the rats in the MI-Sed group, the LVEDP and ±(dp/dt)max of the rats in the MI-Ex group increased (P<0.01), their LVEDP decreased significantly (P<0.01);their myocardial glycogen content increased (P<0.05), their FA and lactic acid content decreased (P<0.01); their PPARα, CPT-1 mRNA and p-AMPKα, GLUT4 and PGC-1αprotein level of myocardium increased significantly (P<0.01). The findings indicate that long-term aerobic exercising improves the metabolic remodeling of a failing heart and enhances cardiac functions by activating AMPK and its downstream signal pathways.