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有氧耐力运动调控大鼠心肌细胞自噬的机制 被引量:1

Mechanism by which aerobic endurance exercise regulates cardiomyocyte autophagy in rats
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摘要 背景:近年来,衰老相关的慢性病研究在世界范围内受到广泛关注,心脏随着年龄增长可能会出现过早衰老,运动作为一种安全健康的干预措施可以延缓其衰老。目的:观察实施规律有氧运动对心肌细胞增龄性老化的影响并探讨其机制。方法:纳入SD大鼠68只,3月龄(青年)20只,13月龄(中年)和22月龄(老年)各24只,每个年龄组再随机均分为静息组及运动组。对3个运动组实施为期10周的递增负荷有氧跑台运动,其中早期递增负荷6周,晚期恒负荷4周;3个静息组不进行有氧运动干预。干预结束后采用实时荧光定量PCR和免疫组化法检测心肌Beclin-1、Ca MKⅡα1、AMPKα1/p AMPKα1和PI3K/Akt/m TOR等通路相关蛋白与基因的表达。结果与结论:(1)实施规律有氧运动后,与青、中、老3个年龄的静息组相比,3个年龄的运动组大鼠心肌细胞自噬Beclin-1表达水平均下调;同时3个年龄的运动组大鼠心肌Ca MKⅡα1 m RNA表达水平也下调;(2)3个年龄静息组p AMPKα1和AMPKα1蛋白表达水平均呈现增龄性趋势;青年、中年和老年运动组的AMPKα1表达水平分别上调16.50%(Ρ<0.05)、63.09%(Ρ<0.01)和31.12%(Ρ<0.01);p AMPKα1表达水平也显著上调,其中青年运动组为131.29%(Ρ<0.01),中年运动组上调40.55%(Ρ<0.01),老年运动组上调16.77%(Ρ<0.05);(3)整体来看,与3个年龄静息组相比,3个年龄运动组大鼠心肌PI3K表达水平均上调,青年、中年运动组AKT1 m RNA表达水平均下调;关于m TOR m RNA表达水平,青年运动组稍下调,中年运动组变化不大,而老年运动组显著上调;(4)提示有氧运动可以显著上调老年组大鼠PI3K的表达,促进m TOR的活性,下调Ca MKⅡα1的表达,下调p AMPKα1/AMPKα1的比值,抑制Beclin-1的表达,调控心肌自噬水平,使其趋向于正常稳定状态,从而延缓心肌衰老。 BACKGROUND:In recent years,studies on chronic diseases related to aging have attra cted wide attention worldwide.As the heart grows with age,premature aging may occur.Exercise is a safe and healthy intervention that can delay its aging.OBJECTIVE:To observe the effect of regular aerobic exercise on the aging of cardiomyocytes and explore its mechanism.METHODS:Healthy male SPF Sprague-Dawley rats aged 3 months(young,n=20),13 months(middle age,n=24),and 22 months(old,n=24)were randomly divided into youth rest group,youth exercise group,middle age rest group,middle age exercise group,old age rest group,and old age exercise group.The three resti ng groups did not do aerobic exercise intervention,and the three exercise groups were given a 10-week incremental load aero bic treadmill exe rcise consisting of 6-week incremental load exe rcise and 4-week constant load exe rcise.RT-PCR and immunohistochemical detection we re used to detect myocardial Beclin-1,Ca MKIIα1,AMPKα1/pAMPKα1,and PI3 K/Akt/mTO R pathway-related proteins and genes.RESULTS AND CONCLUSION:After regular aerobic exercises,compared with the three resting groups,the expression levels of Beclin-1 in cardio myocytes were significantly down-regulated in the three exercise groups.The expression levels of myocardial CaMKIIα1 mRNA were also down-regulated in the three exe rcise gro ups.The protein expression levels of pAMPKal and AMPKα1 in the three resti ng groups showed an aging trend,and the expression levels of AMPKα1 in the young,middle age,and old age exercise groups were up-regulated by 16.50%(P<0.05),63.09%(P<0.05),and 31.12%(P<0.01),respectively.The expression levels of pAMPKα1 were also significantly up-regulated by 131.29%in the young exercise group(P<0.01),40.55%in the middle age exercise group(P<0.01),and 16.77%in the old age exercise group(P<0.05).Overall,the expression levels of PI3K in the myocardium were down-regulated in the three exercise groups compared with the three resting groups,while the expression levels of AKT1 mRNA were down-reg
作者 刘吉焕 王鹏 袁顺灵 简晔 黄少泽 姚思思 刘文锋 Liu Jihuan;Wang Peng;Yuan Shunling;Jian Ye;Huang Shaoze;Yao Sisi;Liu Wenfeng(Hunan Provincial Key Laboratory of Physical Fitness and Exercise Rehabilitation,Hunan Normal University,Changsha 410012,Hunan Province,China;Key Laboratory of Protein Chemistry and Developmental Biology,Ministry of Education,Hunan Normal University,Changsha 410081,Hunan Province,China)
出处 《中国组织工程研究》 CAS 北大核心 2023年第23期3714-3720,共7页 Chinese Journal of Tissue Engineering Research
基金 国家自然科学基金项目(81702236),项目负责人:刘文锋 湖南省教育厅重点项目(20A333),项目负责人:刘文锋 湖南省自然科学基金项目(2018JJ3363),项目负责人:刘文锋 湖南省高校青年骨干教师项目(湘教通[2020]43号),项目负责人:刘文锋 湖南省研究生科研创新项目(湘教通[2021]267号),项目负责人:刘吉焕 湖南师范大学青年优秀人才培养计划(ET1507),项目负责人:刘文锋。
关键词 规律有氧运动 心肌 老化 细胞自噬 AMPK/p AMPK信号通路 regular aerobic exercise myocardium aging autophagy AMPK/pAMPK signaling pathway
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