CAJ | 학술논문

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.
위탐토장기유양운동대만성심력쇠갈대서심기능량대사적조절급가능궤제.장결찰대서관상동맥건립심경후심쇠모형,휴식4주후수궤분위가수술안정조(Sham)、심경안정조(MI-Sed)화심경운동조(MI-Ex),MI-Ex조진행위기8주적포태운동,Sham조화MI-Sed조보지안정상태.실험결속후,좌심실도관법측정혈류동역학삼수,포괄좌심실수축기압력(LVSP)、좌심실서장말기압력(LVEDP)、좌심실압력최대상승속솔(+(dp/dt)max)화좌실압력최대하강속솔((-dp/dt)max);Masson 염색진행심장조직병이학관찰;비색법측정심기당원、지방산(FA)화유산함량;실시형광정량PCR검측심기과양화물매체증식물격활수체α(PPARα)화육감종려선전이매-1(CPT-1)mRNA수평;Western blot법검측심기AMPK、포도당전운단백4(GLUT4)화과양화물매체증식물수체γ공격활인자-lα(PGC-1α)표체수평.결과득도,여Sham조비교,MI-Sed조LVSP、±(dp/dt)max도비상현저성하강(P<0.01),LVEDP칙도비상현저성승고(P<0.01);심기당원함량강저(P<0.01)、FA여유산함량승고(균위P<0.01);심기PPARα화CPT-1 mRNA강저(P<0.01),린산화AMPKα(p-AMPKα)단백수평승고(P<0.05)、GLUT4화PGC-1α단백하강(P<0.01).여MI-Sed조비교,MI-Ex조LVSP、±(dp/dt)max도비상현저성승고(P<0.01),LVEDP칙비상현저성하강(P<0.01);심기당원함량승고(P<0.05),FA 화유산함량하강(P<0.01);심기 PPARα화 CPT-1 mRNA 이급p-AMPKα、GLUT4화PGC-1α단백수평균비상현저성승고(P<0.01).결과표명,장기유양운동통과격활AMPK급기하유신호통로개선료HF심장적대사성중소병제고심공능.
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.