基于胰高血糖素样肽1受体及其下游信号探讨有氧运动对小鼠心梗模型心功能康复的影响

目的:探讨有氧运动训练(AET)对心肌梗死(MI)小鼠的心脏保护作用,并阐明其作用机制是否与胰高血糖素样肽1受体(GLP-1R)激活有关.方法:在实验1(研究AET对MI小鼠的心脏保护作用及对心脏组织中GLP-1R表达的影响)中,67只小鼠分为3组:假手术(sham)组(n=14)、MI组(n=28)和MI+AET组(...

Aerobic exercise induces cardiac rehabilitation in myocardial infarction mice through GLP-1R-AMPK signaling pathway

AIM:To explore the cardioprotective effect of aerobic exercise training(AET)on myocardial infarction(MI)mice,and to clarify whether its mechanism is related to the activation of glucagon-like peptide-1 receptor(GLP-1 R).METHODS:The MI model was established by ligating the anterior descending branch of the left coronary artery in both wild-type and GLP-1 R knockout(GLP-1 R KO)mice,and then subjected to 4-week AET. Echocardiography was used to evaluate mouse cardiac function,and immunohistochemistry was used to detect GLP-1 R expression in the heart tissue. TUNEL staining was used to evaluate myocardial cell apoptosis. DHE fluorescence was used to detect ROS levels in heart tissue. Kit was used to detect myocardial ATP levels. Western blot was used to detect the expression profile of AMPK-mTOR-p70 S6 K signaling pathway and oxidative phosphorylation complexes in heart tissues.RESULTS:AET improved the post-MI survival rate(P<0. 01). Compared with MI group,the ratio of heart weight to tibia length in MI+AET group was reduced by 20. 4%,left ventricular ejection fraction and left ventricular fractional shortening were significantly increased(P<0. 05),and cardiomyocyte apoptosis was reduced(P<0. 05). In addition,the staining area of GLP-1 R in MI+AET group was significantly higher than that in MI group(P<0. 01). Neither the TUNEL-positive nuclei,nor the left ventricular systolic function were significantly different between GLP-1 R KO+MI group and GLP-1 R KO+MI+AET group. In normal mice subjected to MI,AET significantly promoted the activation of AMPK-mTOR-p70 S6 K signaling pathway in cardiac tissues,increased the expression of mitochondrion-encoded genes in complexes Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ,and ATP content,but reduced ROS production. In contrast,GLP-1 R deficiency completely eliminated the cardioprotective effects of AET.CONCLUSION:AET is a cardioprotective strategy against MI injury by improving mitochondrial metabolism,reducing oxidative stress and inhibiting cardiomyocyte apoptosis. Its mechanism is related to mitochondrial energy metabolism and oxidative stress via GLP-1 R-AMPK-dependent mechanism.