间歇运动对心梗大鼠心肌LIF及其受体表征和细胞凋亡的影响

Effects of Interval Exercise on the Expression of Myocardial LIF and LIFR and Cell Apoptosis in a Rat Model with Myocardial Infarction

目的:探讨间歇运动对心肌梗死(myocardial infarction,MI)大鼠心肌细胞凋亡和心肌白血病抑制因子(Leukemia inhibitory factor,LIF)及其受体LIFR表征的影响。方法:3月龄SD雄性大鼠,随机分为假手术组(Sham)、心梗安静组(MI)、心梗+间歇运动组(ME),每组12只。左冠状动脉前降支(Left anterior descending coronary artery,LAD)结扎建立MI模型,ME组采用小动物跑台进行8周间歇训练。训练结束后次日腹腔麻醉,血流动力学方法评定心功能,Masson染色观察分析心肌胶原容积(Collagen volume fraction,CVF)百分比,TUNEL法检测细胞凋亡,Western Blot检测心肌Bcl-2、Bax、LIF、LIFR、p-STAT 3和STAT 3蛋白表达,RT-qPCR检测心肌lif和lifr mRNA表达。结果:心梗大鼠心功能显著降低,心肌纤维化水平和细胞凋亡显著增加。间歇运动可有效改善心梗大鼠心功能,降低心肌纤维化水平,升高Bcl-2/Bax比值,减少TUNEL阳性颗粒,上调心肌LIF及LIFR蛋白与基因的表达和STAT 3磷酸化水平。结论:间歇运动可显著促进心梗大鼠心肌LIF蛋白表达,激活LIF/LIFR/STAT 3通路,抑制心肌细胞凋亡,改善心梗心脏病理重塑和心功能。开展运动干预缺血心脏LIF表征研究与心脏的保护效应,将为心梗患者运动康复手段筛选提供新思路。

Objectives：This study was carried out to determine the effects of interval exercise on myocardial cell apoptosis,expression of Leukemia inhibitory factor（LIF）and its reporter in rat with myocardial infarction（MI）.Methods：Adult male sprague-dawley rats,3-month old,were randomly divided into three groups：Sham-operated group（Sham）,sedentary MI group（MI）and MI with interval exercise group（ME）.The MI model was established by ligation of the left anterior descending（LAD）coronary artery,and rats in ME were subjected to 8weeks interval training.Cardiac function,heart tissue remodeling and cardiomyocyte apoptosis were evaluated after the training.The expression of LIF,LIFR,p-STAT3 and STAT3 was determined in the peri-infarcted area of the left ventricle by Western Blotting or RT-qPCR.Results：MI resulted in cardiac dysfunction and myocardial fibrosis,increasing the degree of myocardial cell apoptosis.Compared with MI group,interval exercise signaficantly improved cardiac function,attenuated myocardial remodeling by reducing CVF% and inhibited cardiomyocyte apoptosis in MI rats.Meanwhile,interval exercise training up-regulated the expression of LIF protein and lif and lifr mRNA,and activated the phosphorylation of STAT 3in myocardium of MI rats.Conclusion：Interval exercise inhibits myocardial cell apoptosis,up-regulates the expression of myocardial LIFs,and activates the signaling pathway of LIF/LIFR/STAT 3after MI.