游泳运动对小鼠心肌梗死的保护作用:基于AMPK/PGC-1α通路

Protective effect of swimming on myocardial infarction:Role of AMPK/PGC-1alpha pathway

目的:阐明游泳运动(SW)激活AMPK/PGC-1α通路减轻小鼠心肌梗死(MI)损伤的作用。方法:选取60只雄性C57BL/6小鼠,随机分为假手术组(Sham)、心肌梗死组(MI)、心肌梗死联合游泳运动组(MI+SW)和心肌梗死联合游泳运动及AMPK抑制剂Compound c组(MI+SW+CC),建立冠状动脉左前降支结扎心肌梗死模型。运动组无负重游泳运动9周。检测左室压力和最大上升与下降速率(±dp/dtmax),观察心脏结构、纤维化、细胞凋亡率以及血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性和肌钙蛋白I(cTnI)含量,检测活性氧(ROS)水平、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和线粒体ATP含量,Western Blot检测Cleaved caspase-3、Cytochrome c、p-AMPK、p-ACC和PGC-1α的蛋白表达。结果:与Sham组比较,MI组左室压力和±dp/dtmax降低(P<0.05),心脏结构紊乱,并出现明显纤维化,血清LDH、CK-MB活性和cTnI含量、细胞凋亡率、ROS和MDA含量增加(P<0.05),ATP含量和SOD活性降低(P<0.05),Cleaved caspase-3和Cytochrome c表达增加而p-AMPK、p-ACC和PGC-1α的表达降低(P<0.05);与MI组比较,MI+SW组左室压力和±dp/dtmax增加,心肌结构改善,纤维化减轻,血清LDH、CK-MB活性和cTnI含量、细胞凋亡率、ROS和MDA含量降低(P<0.05),ATP含量和SOD活性增加(P<0.05),Cleaved caspase-3和Cytochrome c表达降低而p-AMPK、p-ACC和PGC-1α的表达增加(P<0.05);与MI+SW组比较,Compound c可以阻断游泳运动对小鼠心肌梗死后氧化应激和能量代谢的改善以及对AMPK/PGC-1α通路的调控。结论:游泳运动通过调控AMPK/PGC-1α通路抑制氧化应激和改善线粒体能量代谢,减轻小鼠心肌梗死后心肌损伤。

Objective:To investigate the effect of swimming(SW)on myocardial infarction(MI)injury by regulating the AMPK/PGC-1αpathway in mice.Methods:A myocardial infarction model was induced in mice by ligation of the left anterior descending coronary artery.The mice were randomly divided into four groups(n=15):Sham group(Sham),MI group,MI+SW group(MI+SW),and MI+SW+AMPK inhibitor Compound c group(MI+SW+CC).The swimming exercise groups were given none-load swimming training for 9 weeks.The left ventricular pressure,the rate of maximal left ventricular pressure increase(+dp/dtmax),and the rate of maximal left ventricular pressure decrease(-dp/dtmax)were measured.Myocardial structure and fibrosis were observed by HE and Masson's staining.The apoptosis rate,lactate dehydrogenase(LDH)creatine kinase isoenzyme(CK-MB)activities,and troponin I(cTnI)content were observed.The reactive oxygen species(ROS)level,superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,and mitochondrial ATP content were assayed too.Western Blot was used to detect the expression of Cleaved caspase-3,Cytochrome c,p-AMPK,p-ACC,and PGC-1α.Results:Compared with that in the Sham group,the left ventricular pressure and±dp/dtmax in the MI group was significantly decreased.Myocardial fiber arrangement was disordered and ruptured.Myocardial fibrosis,the apoptosis rate,LDH and CK-MB activities,and cTnI content were also increased.The ROS level,MDA content,and mitochondrial ATP content were increased as well as SOD activity was decreased.In addition,the expression of pAMPK,p-ACC,and PGC-1αwas decreased,while the expression of cleaved caspase-3 and cytochrome c was increased.Compared with that in the MI group,the left ventricular pressure and±dp/dtmax in the MI+SW group was significantly increased.Myocardial fiber arrangement,fibrosis,apoptosis rate,LDH and CK-MB activities,and cTnI content were alleviated.The ROS level,MDA content,and mitochondrial ATP content were decreased as well as SOD activity was increased.The expression of p-AMPK,p-ACC,and PGC-1αwas increased.Compound c could block the effect of swimming on MI-induced myocardial injury and the AMPK/PGC-1αpathway after myocardial infarction.Conclusion:Swimming could alleviate cardiac injury after myocardial infarction by inhibiting oxidative stress and improving mitochondrial energy metabolism via the AMPK/PGC-1αpathway in mice.