| 抗阻运动通过刺激骨骼肌FSTL1分泌抑制心梗大鼠心肌细胞凋亡及其机制探讨 |
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| 引用本文： | 郝美丽,席悦,田振军.抗阻运动通过刺激骨骼肌FSTL1分泌抑制心梗大鼠心肌细胞凋亡及其机制探讨[J].体育科学,2020(1):67-78. |
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| 作者姓名： | 郝美丽 席悦 田振军 |
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| 作者单位： | 陕西师范大学体育学院暨运动生物学研究所运动与心血管健康研究室;洛阳师范学院体育学院 |
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| 基金项目： | 国家自然科学基金资助项目(31371199) |
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| 摘 要： | 目的:探讨抗阻运动通过刺激骨骼肌卵泡抑素样蛋白1(Follistatin-like protein 1,FSTL1)分泌,抑制心梗(Myocardial Infarction,MI)大鼠心肌细胞凋亡及其机制。方法:动物实验:结扎SD大鼠左冠状动脉前降支制备MI模型,术后随机分为5组,分别为假手术组(S)、心梗安静对照组(MI)、心梗+抗阻运动组(MR)、心梗+腺相关病毒空载体组(MV)、心梗+FSTL1腺相关病毒载体组(MF),每组10只,其中S组只穿线不结扎。术后1周,MR组进行为期4周的爬梯抗阻运动,MV组和MF组于左后肢胫骨前肌分别注射腺相关病毒空载体和FSTL1腺相关病毒载体。训练结束后次日,腹腔麻醉,测定心功能,摘取心脏和左后肢胫骨前肌。Masson染色观察并计算心肌胶原容积百分比(CVF%);TUNEL检测分析心肌细胞凋亡;Western Blotting实验测定骨骼肌和血清FSTL1蛋白含量,心肌FSTL1、DIP2A、p-Akt/Akt、p-mTOR/mTOR、Bcl2/Bax蛋白表达。细胞实验:H9C2细胞分为8组,即H9C2对照组、H9C2+LPS(脂多糖:Lipopolysaccharide,LPS)组、H9C2+LPS+AICAR(AMPK激动剂AICAR)组、H9C2+LPS+LY294002(PI3K抑制剂LY294002)组、H9C2+LPS+AICAR+LY294002组、H9C2+LPS+rhFSTL1组、H9C2+LPS+rhFSTL1+AICAR组、H9C2+LPS+rhFSTL1+LY294002组。TUNEL检测H9C2细胞凋亡,CCK8检测H9C2细胞存活率,Western Blotting实验检测细胞FSTL1、DIP2A、p-Akt/Akt、p-mTOR/mTOR、Bcl2/Bax蛋白表达。结果:MI后大鼠骨骼肌FSTL1基因和蛋白表达降低,心肌FSTL1基因表达无显著变化,心肌和血清FSTL1蛋白水平显著升高,心肌细胞凋亡和心肌纤维化显著增加,心功能下降。抗阻运动或胫骨前肌注射FSTL1腺相关病毒载体后,骨骼肌、血清和心肌FSTL1蛋白水平均显著升高,心肌FSTL1受体DIP2A、p-Akt、p-mTOR、Bcl2/Bax蛋白表达均显著上调,心肌细胞凋亡和心肌纤维化减少,心功能显著改善,且抗阻运动显著上调骨骼肌FSTL1基因表达,但心肌FSTL1基因表达无显著性差异。FSTL1和AICAR干预均显著抑制LPS诱导的H9C2细胞凋亡,增加FSTL1、DIP2A、p-Akt、p-mTOR、Bcl2/Bax蛋白表达水平和细胞存活率,LY294002干预与上述作用相反。结论:在抗阻运动上调MI大鼠心肌FSTL1表达抑制心肌细胞凋亡过程中,骨骼肌源性FSTL1发挥重要作用,骨骼肌源性FSTL1可通过血液循环到达心脏,与其受体DIP2A结合,激活下游Akt-mTOR信号通路,抑制心肌细胞凋亡,降低心肌纤维化,改善MI大鼠心功能。
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| 关 键 词： | 抗阻运动 骨骼肌 心肌梗死 卵泡抑素样蛋白1 心肌细胞凋亡 H9C2细胞 |
Resistance Exercise Inhibits Cardiomyocyte Apoptosis Through Stimulating the Skeletal Muscle FSTL1 Secretion in Myocardial Infarction Rats and its Mechanisms |
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| HAO Meili,XI Yue,TIAN Zhenjun.Resistance Exercise Inhibits Cardiomyocyte Apoptosis Through Stimulating the Skeletal Muscle FSTL1 Secretion in Myocardial Infarction Rats and its Mechanisms[J].China Sport Science,2020(1):67-78. |
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| Authors: | HAO Meili XI Yue TIAN Zhenjun |
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| Institution: | (Institute of Sports and Exercise Biology,Shaanxi Normal University School of Physical Education,Xi’an 710119,China;Luoyang Normal University,School of Physical Education,Luoyang 471924,China.) |
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| Abstract: | Objective:To investigate the effects of resistance exercise on cardiomyocyte apoptosis through stimulating the skeletal muscle Follistatin-like protein 1(FSTL1)secretion in myocardial infarction rats and its mechanisms.Methods:Animal experiment:the male Sprague-Dawley rats were randomly divided into 5 groups(n=10 in each group):sham-operated group(S),sedentary MI group(MI),MI with resistance exercise group(MR),MI with adeno-associated virus(AAV)empty vector group(MV),and MI with FSTL1-AAV vector group(MF)after the MI model was established by left anterior descending coronary artery ligation.The S group underwent threading without ligation.1 week after MI,rats in MR group were conducted a resistance exercise program for 4 weeks,and rats in MV and MF group were injected AAV empty vector or FSTL1-AAV vector in tibialis anterior of the left limb,respectively.The next day after the whole training program,the heart function was measured after anesthesia,and then the heart and tibialis anterior of the left limb were collected.Collagen volume fraction(%)of myocardium were observed and calculated by Masson staining;cardiomyocyte apoptosis was measured by TUNEL;the protein expression of skeletal muscle and serum FSTL1 and myocardium FSTL1,DIP2A,p-Akt/Akt,p-mTOR/mTOR and Bcl2/Bax were measured by Western blotting.Cell experiment:H9C2 cells were divided into 8 groups:H9C2 cells control group,H9C2+LPS(Lipopolysaccharide)group,H9C2+LPS+AICAR(AMPK activator)group,H9C2+LPS+LY294002(PI3K inhibitor)group,H9C2+LPS+AICAR+LY294002 group,H9C2+LPS+rhFSTL1 group,H9C2+LPS+rhFSTL1+AICAR group,H9C2+LPS+rhFSTL1+LY294002 group.The apoptosis of H9C2 cell was detected by TUNEL;the H9C2 cell viability was determined by CCK8 assay;the protein expression of FSTL1,DIP2A,p-Akt/Akt,p-mTOR/mTOR and Bcl2/Bax in each group were determined by Western blotting.Results:After MI,the skeletal muscle FSTL1 gene and protein expression were decreased,the myocardium and serum FSTL1 protein level were significantly increased,the cardiomyocyte apoptosis and myocardial fibrosis were significantly increased,and the heart function was declined;however,no significant changes were observed in the myocardium FSTL1 gene expression.After resistance exercise or injection of FSTL1-AAV vector,the skeletal muscle and serum FSTL1 protein level and myocardium FSTL1,DIP2A,p-Akt,p-mTOR and Bcl2/Bax protein expression were significantly increased,the cardiomyocyte apoptosis and myocardial fibrosis were decreased and the heart function was significantly improved;meanwhile,resistance exercise significantly up-regulated the FSTL1 gene expression in skeletal muscle,but there was no significant difference in myocardium FSTL1 gene expression.FSTL1 and AICAR inhibited LPS-induced H9C2 cells apoptosis significantly,and increased the FSTL1,DIP2A,p-Akt,p-mTOR,Bcl2/Bax protein expression level and H9C2 cell viability;however,the LY294002 expressed opposite effects.Conclusion:The skeletal muscle-derived FSTL1 plays an important role in resistance exercise up-regulates myocardium FSTL1 expression and inhibited cardiomyocyte apoptosis in MI rats.Skeletal muscle-derived FSTL1 can reach the heart through blood circulation,and then bind to its receptor DIP2A and activate the AktmTOR signaling pathway,which inhibiting the cardiomyocyte apoptosis,reducing myocardial fibrosis and improving heart function in MI rats. |
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| Keywords: | resistance exercise skeletal muscle myocardial infarction Follistatin-like protein 1 cardiomyocyte apoptosis H9C2 cells |
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