运动诱导的生理性心肌肥大中miR-497-3p的表达变化及作用  

The Expression and Effect of miR-497-3p in Exercise-induced Physiological Cardiac Hypertrophy

作　　者：张波 齐洁[2] 张钧[2] Zhang Bo;Qi Jie;Zhang Jun(Puyang Medical College,Puyang 457000,China;Physical Education College of Shanghai Normal University,Shanghai 200234,China)

机构地区：[1]濮阳医学高等专科学校,河南濮阳457000 [2]上海师范大学体育学院,上海200234

出　　处：《中国运动医学杂志》2020年第10期797-803,共7页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金(31571223)。

摘　　要：目的:探讨miR-497-3p、Beclin1在运动性心肌肥大大鼠心肌中的表达变化,及其对运动性心肌肥大发生和发展的影响。方法:选取Sprague-Dawley纯系6周龄雄性大鼠24只,随机分为安静对照组(Con组,n=12)和运动性心肌肥大模型组(Ex组,n=12)。运动性心肌肥大模型组大鼠参照Femandes和Oliveria等制定10周游泳运动训练方案,建立大鼠运动性心肌肥大模型。采用RT-qPCR检测miR-497-3p、心钠素(ANP)、心肌肌球蛋白重链α和β(α-MHC、β-MHC)、α-肌动蛋白(α-actin)、肌浆网钙ATP酶(SERCA2α)及Beclin1的mRNA表达水平,用Western blotting检测自噬相关基因Beclin1的蛋白表达水平。分别用过表达及干扰表达miR-497-3p腺病毒感染H9C2细胞,观察Beclin1的mRNA及蛋白表达水平。通过双荧光素酶报告基因实验验证Beclin1与miR-497-3p的靶向关系。结果:(1)10周游泳运动干预后,Ex组较Con组miR-497-3p表达量显著下降(P<0.01)。(2)10周游泳运动干预后,Ex组较Con组自噬相关蛋白Beclin1的mRNA、蛋白表达水平均显著升高(均P<0.01)。(3)过表达miR-497-3p抑制了自噬相关基因Beclin1的表达(P<0.01),引起心肌自噬水平降低。(4)干扰表达miR-497-3p后,Beclin1 mRNA和蛋白的水平显著上调(均P<0.01)。(5)Beclin1是miR-497-3p的靶基因。结论:10周游泳训练可以通过降低心肌中miR-497-3p的表达,靶向上调Beclin1表达水平,进而引起心肌自噬水平增强,从而诱导运动性心肌肥大形成。Objective To explore the expression of miR-497-3 p and Beclinl in the myocardium of rats with exercise-induced myocardial hypertrophy and their effects on the occurrence and development of such hypertrophy.Methods Twenty-four 6-week-old male Sprague-Dawley rats were randomly divided into a quiet control group(Con,n=12)and an exercise-induced myocardial hypertrophy model group(E x,n=12).The exercise-induced myocardial hypertrophy was induced in rats of Ex group after a 10-week swimming exercise training by referring to Fermandes and Oliveria.The mRNA expression of miR-497-3 p,atrial natriuretic polypeptide(ANP),myosin heavy chainα(α-MHC),myosin heavy chainβ(β-MHC),α-actin,sarcoplasmic reticulum Ca2+-ATPase(SERCA2α)and Beclinl were detected by using quantitative real-time polymerase chain reaction,and the protein expression of Beclinl was detected using Western blotting.The relationship between Beclinl and miR-497-3 p were justified using the double luciferase reporter gene test.Results After the intervention,the average expression of miR-497-3 p in Ex group decreased significantly compared with the Con group,while the mRNA and protein expression of autophagy associated protein Beclinl in Ex group increased significantly(P<0.01 for all).The overexpression of miR-497-3 p inhibited the expression of Beclin1(P<0.01)and decreased the level of autophagy in the myocardium.After the expression of miR-497-3 p was interfered,the mRNA and protein expression of Beclinl increased significantly(P<0.01 for both).Moreover,Beclinl was the target gene of miR-497-3 p.Conclusion The 10-week swimming exercise training can increase the level of myocardial autophagy by lowering the expression of miR-497-3 p and promoting that of Beclinl in myocardium,resulting in myocardial hypertrophy.

关 键 词：运动性心肌肥大 BECLIN1 miR-497-3p 自噬 

分 类 号：R542.2[医药卫生—心血管疾病]