有氧运动通过miR-34a/SIRT1通路调控自噬改善急性心肌梗死大鼠心肌损伤的作用机制OACSTPCD
Mechanism of aerobic exercise ameliorating myocardial injury in rats with acute myocardial infarction by regulating autophagy through miR-34a/SIRT1 pathway
目的 探讨有氧运动改善急性心肌梗死(AMI)大鼠心肌损伤的调控机制.方法 将 24 只雄性SD大鼠随机均分为假手术组、模型组和有氧运动组,每组8 只.通过结扎冠状动脉左前降支构建AMI模型,并对有氧运动组AMI大鼠进行持续4周的有氧运动干预;采用HE染色法和Masson染色法观察各组大鼠的心脏组织学形态和纤维化程度;通过ELISA检测大鼠血浆脑钠肽(BNP)含量;通过经胸超声心动图(TTE)评估缩短分数(FS)、射血分数(EF);RT-qPCR检测miR-34a水平;Western blot(WB)检测自噬相关蛋白的表达.利用H9C2 细胞构建缺氧细胞模型,转染miR-34a抑制剂和siSIRT1,RT-qPCR 检测各组细胞中miR-34a的表达;ELISA检测各组细胞上清液乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)的水平;WB检测各组细胞自噬相关蛋白表达.结果 与模型组相比,有氧运动组的心脏组织形态、纤维化、BNP表达及自噬水平均得到明显改善,且有氧运动组的miR-34a表达下调,差异均有统计学意义(P<0.01);与缺氧+miRNA NC组相比,缺氧+miR-34a抑制剂组的LDH和细胞自噬水平降低,SOD和SIRT1 表达升高(均P<0.01);与缺氧+miR-34a抑制剂+siNC组相比,缺氧+miR-34a抑制剂+siSIRT1 组的LDH和细胞自噬水平升高,而SOD和SIRT1 表达降低(均P<0.01).结论 有氧运动可通过miR-34a/SIRT1 通路抑制心肌细胞自噬水平,进而改善AMI大鼠的心肌损伤.这为研究有氧运动改善AMI心肌损伤提供了新的机制,并且有助于AMI的防治.
Objective To explore the regulatory mechanism of aerobic exercise ameliorating myocardial injury in acute myocardial infarction(AMI)rats.Methods A total of 24 male SD rats were randomly divided into sham-operated group,model group and aerobic exercise group,eight in each group.AMI model was constructed by ligating the left anterior descending branch of the coronary artery.Rats in the aerobic exercise group was subjected to 4 consecutive weeks of aerobic exercise.The histological morphology and degree of fibrosis of rat hearts in all groups were observed by HE staining and Masson staining.The plasma brain natriuretic peptide(BNP)level in rats was detected by enzyme-linked immunosorbent assay(ELISA).Fractional shortening(FS)and ejection fraction(EF)were assessed by transthoracic echocardiography(TTE).The expression of miR-34a was detected by RT-qPCR,and the autophagy related protein expression was analyzed by western blot(WB).The hypoxia cell model was constructed using H9C2 cells,and then transfected with miR-34a inhibitor or siSIRT1.The expression of miR-34a was detected by RT-qPCR.The lactate dehydrogenase(LDH)and superoxide dismutase(SOD)levels in cell supernatant were analyzed by ELISA.The expression of autophagy-related proteins was detected by WB.Results Compared with the model group,the aerobic exercise group showed significant improvement in cardiac tissue morphology,fibrosis,BNP expression,and autophagy level,the expression of miR-34a was down-regulated in the aerobic exercise group,and the differences were statistically significant(P<0.01).Compared with the hypoxia+miRNA NC group,the hypoxia+miR-34a inhibitor group showed down regulation in LDH and autophagy levels,but upregulation in SOD and SIRT1 expressions(all P<0.01).Compared with hypoxia+miR-34a inhibitor+siNC group,hypoxia+miR-34a inhibitor+siSIRT1 group had higher LDH and autophagy levels,and lower SOD and SIRT1 expressions(all P<0.01).Conclusion Aerobic exercise can inhibit cardiomyocyte autophagy levels via miR-34a/SIRT1 pathway,thereby ameliorates myocardial injury in AMI rats.This provides a new mechanism to study the improvement of myocardial injury in AMI by aerobic exercise and contributes to the prevention and treatment of AMI.
吴爱萍;朱悦红;夏婉;章睿
310013 杭州,浙江医院康复医学科
急性心肌梗死有氧运动自噬微小RNA-34a
Acute myocardial infarctionAerobic exerciseAutophagyMiR-34a
《心脑血管病防治》 2024 (005)
13-18,51 / 7
浙江省医药卫生科技计划项目(2019KY002);浙江省中医药科技计划项目(2020ZB004)
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