运动诱导的miR-126对糖尿病小鼠心肌的保护作用及机制研究  

Mechanisms Underlying the Protective Effects of Exercise-Induced MiR-126 on Myocardium of db/db Mice

作　　者：柳华[1] 孙静[1] 于晓涵 杨翼[1] LIU Hua;SUN Jing;YU Xiaohan;YANG Yi(Wuhan Sports University,Wuhan 430079,China)

机构地区：[1]武汉体育学院,湖北武汉430079

出　　处：《中国体育科技》2022年第6期74-80,共7页China Sport Science and Technology

基　　金：国家自然科学基金项目(81700280);湖北省自然科学基金项目(2017CFB361);武汉体育学院青年基金项目(2019Z01);武汉体育学院科研团队项目(18QTD04)。

摘　　要：目的:探讨不同强度有氧运动诱导的miR-126对2型糖尿病db/db小鼠心肌的保护作用及其机制。方法:16周龄雄性m/m和db/db小鼠分为5组,m/m小鼠正常对照组(sham组)、db/db小鼠分为空白对照组(NC组)、小强度运动组(LE组)、中强度运动组(ME组)和大强度运动组(HE组),每组各6只。LE、ME和HE组进行8周跑台运动,每周5次,每次30 min。运动强度分别为:LE组5 m/min,ME组10 m/min,HE组15 m/min,坡度均为0。最后一次运动后24 h取血清和心肌组织,测空腹血糖水平、空腹血清胰岛素水平、血压和心率。心肌组织分别进行电镜、α-SMA染色、WGA-AF488染色和DHE染色观察。RT-PCR检测血清和心肌miR-126表达量;Western Blot检测心肌SPRED1、VEGF和NF-κB蛋白表达量。结果:与NC组比较,LE、ME和HE组有氧运动8周后空腹血糖、空腹血清胰岛素、血压(收缩压和舒张压)和心率显著降低。电镜下NC组心肌出现肌丝溶解断裂、线粒体肿胀等病理变化,而ME组有明显改善。DHE染色显示ROS产生,WGA-AF488染色显示心肌肥大,α-SMA染色显示血管密度,LE、ME和HE组较之NC组均显著改善。与sham组相比,NC组血清和心肌miR-126表达量降低,但运动后LE、ME和HE组表达均显著上升。运动后LE、ME和HE组心肌NF-κB蛋白表达量均明显降低,ME组SPRED1蛋白表达量显著降低,而3个运动组VEGF蛋白表达量均显著升高。结论:8周有氧耐力运动可明显改善糖尿病db/db小鼠的血糖和胰岛素水平,减少心肌炎症反应,提高心肌血管再生,其中以ME组的效果最为显著,其保护机制与miR-126/NF-κB和miR-126/SPRED1/VEGF信号通路相关。Objective:To explore the protective effects and underlying mechanisms of different intensity exercise interventions-induced miR-126 on myocardium of db/db mice.Methods:Male 16-week-old m/m mice and db/db mice were randomly divided into five groups including sham group,negative control(NC)group,low intensity exercise(LE)group,medium intensity exercise(ME)group and high intensity exercise(HE)group,6 in each group.The exercise mice were given treadmill exercise for 30 min five times a week for 8 weeks.The intensity of exercise was 5 m/min,10 m/min and 15 m/min,respectively.The serum and myocardial tissue of the three groups were sampled.24 h post-exercise,the blood pressure,heart rate,fasting blood glucose(FBG)level and fasting serum insulin(FINS)level were measured.Myocardial tissue was observed by electron microscopy,DHE,WGA-AF488 and alpha-SMA fluorescence staining.The expression levels of microRNA-126 in serum and myocardium were detected by realtime PCR.The expression levels of NF-κB,SPRED1 and VEGF in myocardium were detected by Western Blot.Results:After 8 weeks of aerobic endurance exercise,the systolic and diastolic blood pressures,heart rate,FBG level,and FINS level in LE,ME and HE groups were significantly lower than those in NC group.Under the electron microscope,myofilament was dissolved and mitochondria swelled in the NC group,which were significantly improved in ME group.DHE staining,WGA-AF488 staining and alpha-SMA staining showed that ROS relative fluorescence intensity,the area of myocardial cells and myocardial vascular density were significantly improved in exercise groups.The expression levels of circulating microRNA-126 and myocardial microRNA-126 in serum and myocardial tissue in NC group were significantly lower than those in sham group,while those in exercise groups were significantly higher.The expression levels of NF-κB protein in myocardium in exercise groups were significantly decreased and SPRED1 in ME group was significantly decreased,while those of VEGF protein in exercise groups we

关 键 词：有氧运动 DB/DB小鼠 MIR-126 SPRED1 糖尿病心肌病 

分 类 号：G804.2[文化科学—运动人体科学]