Exercise training reduces ventricular arrhythmias through restoring calcium handling and sympathetic tone in myocardial infarction mice
Exercise training reduces ventricular arrhythmias through restoring calcium handling and sympathetic tone in myocardial infarction mice
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DOI：
10.14814/phy2.13972
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发表时间：
2019-02
影响因子：
2.5
通讯作者：
Rujie Qin;N. Murakoshi;DongZhu Xu;K. Tajiri;D. Feng;E. Stujanna;Saori Yonebayashi;Y. Nakagawa;H. Shimano;A. Nogami;A. Koike;K. Aonuma;M. Ieda
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作者：
Rujie Qin;N. Murakoshi;DongZhu Xu;K. Tajiri;D. Feng;E. Stujanna;Saori Yonebayashi;Y. Nakagawa;H. Shimano;A. Nogami;A. Koike;K. Aonuma;M. Ieda
运动可以改善心力衰竭患者的发病率和死亡率；然而，其潜在的机制仍有待充分研究。因此，我们研究了运动对心肌梗死(MI)所致心力衰竭小鼠心功能和室性心律失常的影响。野生型雄性小鼠采用假手术或永久结扎左冠状动脉造成心肌梗死。MI小鼠分为安静组和两个干预组：MI-Ex组(进行6周的跑台运动训练)和MI-βb组(口服比索洛尔1 mg/kg/d，不进行运动)。超声心动图和组织学检查评价心功能和心结构。以运动能力和心肺功能作为运动峰值耗氧量(峰值VO2)。通过遥测记录评价自主神经系统功能和自发性室性心律失常的发生率。用实时荧光定量聚合酶链式反应和Western blotting检测左心室(LV)的mRNA和蛋白表达。两组在存活率、心肌梗死大小、心功能和结构方面无差异，而运动训练提高了峰值VO2。与MI-SED相比，MI-Ex和MI-βb交感神经张力降低，自发性室性心律失常发生率降低。Western印迹结果显示，运动和β阻滞剂可使CaMKII和RyR2的过度磷酸化得到恢复。此外，运动和β阻滞剂可使miR-1表达增加和靶蛋白PP2A表达降低。持续的大强度运动训练可以通过恢复自主神经失衡和受损的钙处理来抑制亚急性期和慢性期的室性心律失常，类似于β阻滞剂的作用。
Exercise can improve morbidity and mortality in heart failure patients; however, the underlying mechanisms remain to be fully investigated. Thus, we investigated the effects of exercise on cardiac function and ventricular arrhythmias in myocardial infarction (MI) induced heart failure mice. Wild‐type male mice underwent sham‐operation or permanent left coronary artery ligation to induce MI. MI mice were divided into a sedentary (MI‐Sed) and two intervention groups: MI‐Ex (underwent 6‐week treadmill exercise training) and MI‐βb (oral bisoprolol treatment (1 mg/kg/d) without exercise). Cardiac function and structure were assessed by echocardiography and histology. Exercise capacity and cardiopulmonary function was accepted as oxygen consumption at peak exercise (peak VO2). Autonomic nervous system function and the incidence of spontaneous ventricular arrhythmia were evaluated via telemetry recording. mRNA and protein expressions in the left ventricle (LV) were investigated by real‐time PCR and Western blotting. There were no differences in survival rate, MI size, cardiac function and structure, while exercise training improved peak VO2. Compared with MI‐Sed, MI‐Ex, and MI‐βb showed decreased sympathetic tone and lower incidence of spontaneous ventricular arrhythmia. By Western blot, the hyperphosphorylation of CaMKII and RyR2 were restored by exercise and β‐blocker treatment. Furthermore, elevated expression of miR‐1 and decreased expression of its target protein PP2A were recovered by exercise and β‐blocker treatment. Continuous intensive exercise training can suppress ventricular arrhythmias in subacute to chronic phase of MI through restoring autonomic imbalance and impaired calcium handling, similarly to that for β‐blockers.