间歇运动激活miR-34a/SIRT1/Trx-1通路抑制心梗大鼠肾脏氧化应激保护肾功能  

Aerobic interval training activates miR-34a-SIRT1-Trx-1 signaling pathway,inhibits renal oxidative stress and improves renal function in a rat model with myocardial infarction

作　　者：耿元文[1] 林琴琴[1] 王湘怡 李若明 田振军[2] GENG Yuanwen;LIN Qingqin;WANG Xiangyi;LI Ruoming;TIAN Zhenjun(School of Physical Education,Yanshan University,Qinhuangdao 066004,Hebei,China;Shaanxi Normal University,Xi'an 710062,Shaanxi,China)

机构地区：[1]燕山大学体育学院,河北秦皇岛066004 [2]陕西师范大学体育学院,陕西西安710062

出　　处：《山东体育学院学报》2020年第6期44-53,共10页Journal of Shandong Sport University

基　　金：国家自然科学基金(31300978);河北省自然科学基金(C2019203537);河北省高等学校科学技术研究项目(QN2019068)。

摘　　要：目的:探讨间歇运动激活心梗(myocardial infarction,MI)大鼠肾脏miR-34a/SIRT1/Trx-1通路抑制肾脏氧化应激反应改善肾脏功能的作用。方法:3月龄雄性SD大鼠,随机分为假手术组(Sham)、心肌梗死组(MI)和心梗+间歇有氧运动组(ME),每组12只。MI组采用心脏左冠状动脉前降支(LAD)结扎法建立MI模型。Sham组大鼠实施假手术,ME组大鼠在MI手术后1周进行4周跑台运动。ME组适应性训练1周(10~15 m/min,30 min/d,共5 d)。正式训练起始速度10 min×10 m/min(40%~50%VO_(2) max)热身,以7 min×25 m/min(85%~90%VO_(2) max)和3 min×15 m/min(50%~60%VO_(2) max)交替进行大中等强度间歇运动。总时间为60 min,每周训练5 d,连续训练4 w。训练结束后次日取材,测定各组大鼠心电图变化,采用紫外分光光度法测定肾脏MDA含量、T-AOC和GSH-Px活性,ELISA法测定肾脏LDH活性、血清Trx-1水平以及血清和尿液NAG水平,RT-qPCR检测肾脏miR-34a和Trx-1表达变化,Western Blot检测肾脏SIRT1、SOD1、SOD2、NOX2和NOX4蛋白表达。结果:与Sham组比较,MI组大鼠肾脏MDA含量和LDH活性显著增加,T-AOC和GSH-Px活性显著降低;肾脏miR-34a表达显著增加,SIRT1、SOD1和SOD2表达显著减少,NOX2和NOX4表达显著增加;肾脏Trx-1 mRNA表达增多,血清Trx-1水平升高,血清及尿液NAG表达显著升高。与MI组比较,间歇运动显著降低MI大鼠肾脏MDA含量和LDH活性,增加T-AOC和GSH-Px活性,上调SIRT1、SOD1、SOD2和Trx-1的表达,抑制NOX2、NOX4和miR-34a表达,降低血清及尿液NAG表达。血清Trx-1与NAG表达呈显著正相关;肾脏SIRT1蛋白表达与NOX2、NOX4、MDA和LDH表达呈显著负相关;与SOD1、SOD2、T-AOC和GSH-Px表达呈显著正相关。肾脏miR-34a表达与SIRT1表达呈显著负相关,与MDA和LDH蛋白表达呈显著正相关,与SOD1、SOD2、T-AOC和GSH-Px表达呈显著负相关。结论:间歇运动抑制MI大鼠肾脏miR-34a表达,激活其下游SIRT1/Trx-1调控的NOX4信号通路。表明,miR-34a/SIRT1/Trx-1信号Objective:To determine the effects of aerobic interval training(AIT)on the expressions of microRNA-34 a(miR-34 a),SIRT1 and Trx-1 and renal oxidative stress in rats with myocardial infarction(MI).Methods:male Sprague Dawley rats were randomly divided into Sham-operated group(Sham),Sedentary MI group(MI)and MI with AIT group(ME)(n=12).The MI model was established by ligation the left anterior descending coronary artery(LAD).Rats in ME were subjected to 8 weeks treadmill exercise training.(AIT:60 min/day with 10 min of warm-up at 10 m/min(40%~50%VO_(2) max)and 50 min of exercise at 25 m/min 7 min(85%~90%VO_(2) max)interspersed with 3 min at 15 m/min(50%~60%VO_(2) max)).After training renal function was evaluated.The levels of renal MDA content,T-AOC and GSH-Px activity by ultraviolet spectrophotometry.The activity of LDH in renal was determined by microplate assay.The levels of serumrx-1 and serum,urine NAG were assessed by ELISA.The expression of renal miR-34 a,Trx-1 was examined by RT-q PCR.The expression of renal SIRT1 protein was examined by western blotting.Results:Compared with the Sham group,MI increased the expression of renal MDA,LDH,NOX2,NOX4,Trx-1 mRNA and the level of serum Trx-1,serum and urine NAG,and the expression of renal miR-34 a.Meanwhile,MI inhibited the expression of renal T-AOC,GSH-Px,SIRT1,SOD1 and SOD2.Compared with the MI group,AIT inhibited the expression of renal MDA,LDH,NOX2,NOX4,serum and urine NAG and the expression of renal miR-34 a.Meanwhile,AIT up-regulated the expression of renal T-AOC,GSH-Px,SIRT1,SOD1,SOD2 and renal Trx-1 mRNA and the level of serum Trx-1.The serum level of Trx-1 was positively related to the level of NAG.The expression of SIRT1 protein was negatively related to the expression of NOX2,NOX4,MDA and LDH,and positively related to the xpression of SOD1,SOD2,T-AOC and GSH-Px.The expression of miR-34 a was negatively related to the expression of SIRT1,SOD1,SOD2,T-AOC and GSH-Px protein,and positively related to the expression of MDA and LDH.Conclusion:AIT inhibits the

关 键 词：间歇运动 心肌梗死 氧化应激 MIR-34A SIRT1 

分 类 号：G804.2[文化科学—运动人体科学]