史清钊　陈怡月　王智强　李丁丁　于海燕　姚政立　王蕴红

摘 要： 探讨运动诱发心肌适应过程中是否有心肌内质网应激的参与。方法：大鼠进行跑台耐力训练，建立不同训练强度、不同训练时间和周期的大鼠运动模型，在末次训练结束后24 h取材，取左室心肌，采用western blot检测内质网应激相关蛋白GRP78、GRP94、ERP72和CHOP的表达。结果：1）5周运动模型组：时间递增组大鼠心肌GRP78较安静组显著升高，GRP94、ERP72、CHOP蛋白表达无显著性差异；恒时恒速组、速度递增组大鼠心肌GRP78、GRP94、ERP72、CHOP蛋白表达较安静组未见显著性差异。2）10周运动模型：恒时恒速组、速度递增组大鼠心肌GRP78、GRP94、ERP72、CHOP蛋白表达较安静组无显著差异。结论：以延长运动持续时间为特征的5周耐力训练诱发GRP78蛋白表达升高，而速度恒定或速度递增的耐力训练没有诱发心肌与内质网应激相关的蛋白表达，提示运动方式可能与心肌内质网应激有关。

关键词：运动；心肌；内质网应激；葡萄糖调节蛋白78

中图分类号：G 804.2 学科代码：040302 文献标识码：A

Abstract：Objective： To explore whether endoplasmic reticulum stress is involved in the process of exercise-induced myocardial adaptation. Methods： Rats were subjected to treadmill exercise training with different exercise intensity， duration and exercise program， and then euthanized 24h after last run. GRP78， GRP94 and ERP72 expressions in myocardium of left ventricular were measured with western blot analysis. Results： 1） there was a significant increase in the GRP78 expression but no significant difference in the expression of GRP94， ERP72， CHOP in duration-increase group. No significant changes in the expression of GRP78， GRP94， ERP72 and CHOP protein expressions in rats undergoing constant speed and speed-increase training were observed in all rats of 5-week trained groups； 2） No significant changes in the expression of GRP78， GRP94， ERP72 and CHOP were observed in all rats of 10-week trained groups when compared with age-matched control group. Conclusion： GRP78 expression was induced in rat myocardium after five-week duration-increase endurance training， while no significant change in GRP78 expression was observed after constant speed or speed-increase training. It suggests that exercise mode might be associated with exercise-induced endoplasmic reticulum stress.

Keywords： exercise； cardiac muscle； endoplasmic reticulum （ER）；glucose-regulated protein 78

內质网应激反应（ERS）可由缺氧、供能状态变化及生长刺激因子等生理因素启动，适度的内质网应激反应，能够提高对应激刺激的耐受力，有利于细胞内钙和蛋白质加工等稳态的恢复 [1-4]。研究表明，阻抗运动能够诱发骨骼肌内质网应激信号通路的激活，提示内质网应激与运动适应有密切关系[5]；但有关运动诱发心肌内质网应激的研究还鲜见报道。已有研究证明，内质网应激参与了压力超负荷、机械应力等引起心肌损伤和心肌肥大的发生发展[6]，并且我们前期的研究也显示，长时间的耐力运动导致与内质网应激相关的eIF2/ATF4信号通路激活[7]，提示运动可能引起心肌的内质网应激。……