Qin Rujie, Murakoshi Nobuyuki, Xu DongZhu, Tajiri Kazuko, Feng Duo, Stujanna Endin N, Yonebayashi Saori, Nakagawa Yoshimi, Shimano Hitoshi, Nogami Akihiko, Koike Akira, Aonuma Kazutaka, Ieda Masaki
Department of Cardiology, Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Physiol Rep. 2019 Feb;7(4):e13972. doi: 10.14814/phy2.13972.
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 VO ). 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 VO . 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.
运动可改善心力衰竭患者的发病率和死亡率；然而，其潜在机制仍有待充分研究。因此，我们研究了运动对心肌梗死（MI）诱导的心力衰竭小鼠心脏功能和室性心律失常的影响。野生型雄性小鼠接受假手术或永久性左冠状动脉结扎以诱导MI。MI小鼠分为久坐组（MI-Sed）和两个干预组：MI-Ex（进行6周跑步机运动训练）和MI-βb（口服比索洛尔治疗（1mg/kg/d）且不运动）。通过超声心动图和组织学评估心脏功能和结构。运动能力和心肺功能以运动峰值时的耗氧量（峰值VO）来衡量。通过遥测记录评估自主神经系统功能和自发性室性心律失常的发生率。通过实时PCR和蛋白质印迹法研究左心室（LV）中的mRNA和蛋白质表达。生存率、MI大小、心脏功能和结构方面无差异，但运动训练改善了峰值VO。与MI-Sed相比，MI-Ex和MI-βb的交感神经张力降低，自发性室性心律失常的发生率较低。通过蛋白质印迹法，运动和β受体阻滞剂治疗可恢复CaMKII和RyR2的过度磷酸化。此外，运动和β受体阻滞剂治疗可恢复miR-1表达升高及其靶蛋白PP2A表达降低的情况。持续的强化运动训练可通过恢复自主神经失衡和受损的钙处理来抑制MI亚急性期至慢性期的室性心律失常，这与β受体阻滞剂的作用类似。
