有氧运动调控线粒体质量控制系统逆转衰老大鼠心脏的病理性重塑

Aerobic exercise modulates mitochondrial quality control system to reverse cardiac pathological remodeling in aging rats

背景:衰老与心血管疾病易感性增加有关,而线粒体功能障碍在各种原因所致心血管疾病的发病机制中起关键作用。规律体力活动有益心血管健康并能够防治慢性心脏疾病,然而线粒体在运动对衰老心脏发挥保护作用中的具体机制尚未明确。目的:观察有氧运动对衰老大鼠心脏病理性重塑的影响,并探讨线粒体质量控制系统在其间的可能作用机制。方法:取60只Wistar大鼠,采用随机数字表法分3组,每组20只:青年安静组(6月龄)和老年安静组(20月龄)大鼠在鼠笼内饲养12周,老年运动组(20月龄)大鼠进行12周中等强度的有氧跑台运动(60%最高跑速,坡度0°,60 min/d,5 d/周)。12周后,取大鼠心脏进行相关指标检测。结果与结论:①组织学检测:与青年安静组比较,老年安静组大鼠出现心脏向心性肥大、心肌纤维化及心肌细胞凋亡和缺失、心脏舒张功能障碍(P<0.05);与老年安静组比较,老年运动组大鼠心肌纤维化和细胞凋亡率减轻、细胞数量增加、心功能改善(P<0.05),心脏表型由病理性肥大向生理性肥大转变;②心肌线粒体功能:与青年安静组比较,老年安静组大鼠心肌线粒体过氧化氢生成速率增加(P<0.05),态3、态4呼吸速率和呼吸控制比下降(P<0.05),呼吸链复合体Ⅰ、Ⅱ和Ⅳ活性下降(P<0.05),线粒体钙保留能力下降(P<0.05)、线粒体通透性转换孔开放程度增加(P<0.05);与老年安静组比较,老年运动组大鼠上述指标均有明显改善(P<0.05);③心肌线粒体质量控制:与青年安静组比较,老年安静组大鼠心肌线粒体生物合成下降(P<0.05),线粒体自噬活性增加(P<0.05),线粒体融合减少(P<0.05)、分裂增加(P<0.05);与老年安静组比较,老年运动组线粒体生物合成和线粒体自噬活性升高(P<0.05),线粒体融合增加(P<0.05)、分裂减少(P<0.05);④结果表明:规律有氧运动通过调控线粒体质量控制系统发挥对衰老大鼠的心脏保护效应,进而逆转病理性心脏重塑并提升心功能。

BACKGROUND:Aging is associated with increased susceptibility to cardiovascular disease,and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease.Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease.However,the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified.OBJECTIVE:To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system.METHODS:Sixty Wistar rats were randomly divided into young sedentary group(6 months old),old sedentary group(20 months old)and old exercise group(20 months old)with 20 rats in each group.Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks,while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise(60%of the maximal running speed,slope 0°,60 minute per day,5 days per week)for 12 weeks.After the experiment,the heart was extracted for relevant indicator tests.RESULTS AND CONCLUSION:Cardiac morphology and myocardial histopathology:compared with the young sedentary group,the rats in the old sedentary group presented with concentric cardiac hypertrophy,myocardial fibrosis,myocardial cell apoptosis and loss,and cardiac diastolic dysfunction(P<0.05);compared with the old sedentary group,animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates,increased cell numbers,improved cardiac function(P<0.05),and a transition in cardiac phenotype from pathological to physiological hypertrophy.Mitochondrial function:compared with the young sedentary group,the generation rate of mitochondrial hydrogen peroxide increased(P<0.05),respiration rate and respiratory control ratio of state 3 and state 4 decreased(P<0.05),activities of respiratory chain complexes I,II and IV decreased(P<0.05),mitochondrial calcium retention capacity decreased(P<0.05),and mitochondrial permeability transition pore opening increased(P<0.05)in the old sedentary group.Compared with the old sedentary group,all of the above indicators were significantly improved in the old exercise group(P<0.05).Mitochondrial quality control:compared with the young sedentary group,mitochondrial biogenesis decreased(P<0.05),mitophagy activity increased(P<0.05),mitochondrial fusion reduced(P<0.05),and fission raised(P<0.05)in the old sedentary group;compared with the old sedentary group,mitochondrial biogenesis and mitophagy activity increased(P<0.05),mitochondrial fusion raised(P<0.05)and fission decreased(P<0.05)in the old exercise group.To conclude,regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system,thus reversing pathological cardiac remodeling and improving cardiac function.