有氧间歇运动对2型糖尿病大鼠心肌线粒体自噬的影响  

Effects of aerobic interval training on autophagy of myocardial mitochondria in type 2 diabetic rats

作　　者：侯改霞[1] 习雪峰[1] 刘倩倩[1] 付素焕 唐书曼 卞寒雪 HOU Gai-xia;XI Xue-feng;LIU Qian-qian;FU Su-huan;TANG Shu-man;BIAN Han-xue(College of Physical Education,Henan University,Kaifeng 475001,China)

机构地区：[1]河南大学体育学院,河南开封475001

出　　处：《中国病理生理杂志》2022年第3期442-447,共6页Chinese Journal of Pathophysiology

基　　金：河南省重点研发与推广专项(科技攻关)项目(No.202102310318,No.212102310262);河南省高等学校重点科研项目(No.20A890002)。

摘　　要：目的:探讨线粒体自噬在运动(Exe)干预2型糖尿病心肌病中的作用及可能机制。方法:自发性2型糖尿病Goto-Kakizaki(GK)大鼠随机分为2组:糖尿病组(GK组)和GK+Exe组,每组8只;另增设8只同周龄雄性Wistar大鼠作为对照组(Wistar组)。GK+Exe组大鼠经有氧间歇运动干预8周,每天60 min,每周5 d。在最后一次运动结束48 h后,过夜禁食12 h后,将大鼠腹腔麻醉、剖腹,腹主动脉采血,检测空腹血糖(FBG)、空腹胰岛素(FINS)及血清乳酸脱氢酶(LDH)和肌酸激酶(CK)水平。制作心肌透射电子显微镜切片,观察心肌细胞及线粒体的超微结构。Western blot法测定心肌组织中p-AMPK、p-ULK1、TFEB、PINK1、parkin、LC3-Ⅱ、LC3-Ⅰ和p62蛋白表达,并计算LC3-Ⅱ/LC3-Ⅰ比值。结果:与Wistar组相比,GK组大鼠FBG及血清LDH和CK水平显著升高(P<0.01),FINS水平显著降低(P<0.01);心肌线粒体结构欠缺,有空泡现象,偶见自噬体;心肌p-ULK1表达显著下降(P<0.01),p62表达显著升高(P<0.01)。与GK组相比,GK+Exe组大鼠FBG和血清CK水平显著降低(P<0.05),FINS水平显著升高(P<0.05);心肌线粒体结构基本完整,空泡现象减轻,自噬体形成增多;心肌p-AMPK、p-ULK1、TFEB和parkin表达及LC3-Ⅱ/LC3-Ⅰ显著升高(P<0.05或P<0.01),p62表达显著下降(P<0.05)。结论:有氧间歇运动对2型糖尿病心肌病具有一定的缓解作用,其机制可能与激活心肌AMPK/ULK1信号通路,提高心肌线粒体自噬有关。AIM:To investigate the effect of exercise(Exe)intervention on type 2 diabetic cardiomyopathy and its possible mechanism.METHODS:Spontaneously type 2 diabetic Goto-Kakizaki(GK)rats were randomly divided into diabetic group(GK group)and GK+Exe group,while another 8 male Wistar rats served as control group(Wistar group).The rats in GK+Exe group were treated with aerobic interval training,60 min per day,5 d per week for 8 weeks.The rats were anesthetized,and the blood was collected 48 h after the last Exe with overnight fasting.Fasting blood glucose(FBG),fasting inslulin(FINS),and serum LDH and CK levels were measured.Ultrastructure of cardiomyocytes and mitochondria was observed by transmission electron microscopy.The protein levels of p-AMPK,p-ULK1,TFEB,PINK1,parkin,LC3-Ⅱ,LC3-Ⅰ and p62 in myocardial tissues were measured by Western blot,and the ratio of LC3-Ⅱ/LC3-Ⅰ was calculated.RESULTS:Compared with Wistar group,the FBG,and serum LDH and CK levels were increased in GK group(P<0.01),and FINS in GK group was decreased significantly(P<0.01).Incomplete mitochondrial structure,vacuole and occasional autophagy were observed in the myocardial mitochondria of GK rats.The expression of p-ULK1 was decreased,while p62 was increased in GK group(P<0.01).Compared with GK group,the FBG and serum CK levels were decreased,while FINS was increased significantly in GK+Exe group(P<0.05).Normal mitochondrial structure,less vacuoles and more autophagosomes were observed in GK+Exe group.Exe also elevated the levels of p-AMPK,p-ULK1,TFEB,parkin and LC3-Ⅱ/LC3-Ⅰ,but inhibited p62 expression(P<0.05).CONCLUSION:Aerobic interval training attenuates type 2 diabetic cardiomyopathy through AMPK/ULK1 signaling pathway and myocardial mitochondrial autophagy.

关 键 词：糖尿病心肌病 有氧间歇运动 线粒体自噬 AMPK/ULK1信号通路 

分 类 号：R587.2[医药卫生—内分泌] R363.2[医药卫生—内科学]