不同运动方式上调FSTL1蛋白表达诱导心梗心脏血管新生
Different Exercise Modes Up-regulate FSTL1 and Induce Angiogenesis in the Heart with Myocardial Infarction
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摘要: 目的:探讨不同运动方式对内源性卵泡抑素样蛋白1(FSTL1)诱导心梗心脏血管新生的作用。方法:雄性SD大鼠随机分为假心梗组(S)、心梗安静组(MI)、心梗+间歇运动组(ME)、心梗+抗阻训练组(MR)和心梗+机械振动组(MV),每组12只。左冠状动脉前降支结扎制备心梗模型。ME组、MR组和MV组分别采用小动物跑台、负重爬梯和小动物振动台3种方式进行为期4周的训练。训练结束后采用免疫荧光染色法定位FSTL1蛋白表达并进行新生血管观察与分析,RT-qPCR和WB法检测心肌FSTL1基因与蛋白表达,血流动力学法评定心功能,Masson染色观察分析心肌胶原面积百分比(CVF)。结果:心梗导致心肌FSTL1蛋白表达上调,且出现内皮细胞增殖和血管新生,心肌fstl1基因表达不受心梗病理条件或运动方式的影响。不同运动方式均可进一步提高心肌FSTL1蛋白表达,显著促进内皮细胞增殖和血管新生,抗阻训练效果最显著,间歇运动次之,而机械振动效果最弱。不同运动方式均可降低CVF,有效改善心功能。结论:不同运动方式可有效刺激心梗心脏内源性FSTL1表达增加,促进心肌血管新生,降低心梗心肌纤维化,改善心功能,其中,抗阻训练的效果较间歇运动和机械振动更显著。探索不同运动方式对心梗心脏保护效应的差异,将为心梗心脏的运动康复机制研究和运动处方筛选与制定提供实验依据。Abstract: Objectives:The aim of this study is to investigate the effects of different exercise modes on endogenous follistatin like-1(FSTL1)induced angiogenesis in the heart with myocardial infarction(MI).Methods:3-month old adult male sprague-dawley rats were randomly divided into 5groups(n=12):Sham-operated group(S),sedentary MI group(MI),MI with interval exercise group(ME),MI with resistance training group(MR)and MI with mechanical vibration group(MV).The MI model was established by ligation of the left anterior descending(LAD)coronary artery.Rats in ME,MR and MV group were underwent 4weeks' training using small animal treadmill,weighted climbing up ladder and small animal vibrating platform,respectively.FSTL1 protein location and neovascularization were observed and analyzed by immunofluorescence staining;FSTL1gene and protein expression were measured by RT-qPCR and Western blot;Heart function was evaluated by hemodynamics;Collagen volume fraction(CVF)of myocardium was observed and analyzed by Masson's trichrome staining.Results:MI resulted in the up-regulation of myocardium FSTL1,endothelial cell(EC)proliferation and angiogenesis.Myocardial fstl1 gene expression was not affected by MI pathological conditions or exercise modes.Different exercise modes could further increase myocardial FSTL1 protein expression,significantly improve EC proliferation and angiogenesis.The effect of resistance training was more significant than interval exercise,and the mechanical vibration was the weakest.The CVF was reduced and the heart function was effectively improved by different exercise modes after MI.Conclusion:Different exercise modes effectively stimulate endogenous FSTL1 expression and myocardial angiogenesis,decrease myocardial fibrosis and improve heart function after MI.The effect of resistance training is better than interval exercise and mechanical vibration.Comparing the effects of different exercise modes on MI heart protection will provide the experimental basis for exercise rehabilitative mechanism research and the filtration and formulation of exercise prescription of MI patient.