Wang Hui, Bei Yihua, Lu Yan, Sun Wei, Liu Qi, Wang Yalong, Cao Yujie, Chen Ping, Xiao Junjie, Kong Xiangqing
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2015;35(6):2159-68. doi: 10.1159/000374021. Epub 2015 Apr 7.
BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) represents the major cause of morbidity and mortality among diabetics. Exercise has been reported to be effective to protect the heart from cardiac injury during the development of DCM. However, the potential cardioprotective effect of exercise in advanced DCM remains unclear.
Seven-week old male C57BL/6 wild-type or db/db mice were either subjected to a running exercise program for 15 weeks or kept sedentary. Cardiac function, myocardial apoptosis and fibrosis, and mitochondrial biogenesis were examined for evaluation of cardiac injury.
A reduction in ejection fraction and fractional shortening in db/db mice was significantly reversed by exercise training. DCM induced remarkable cardiomyocyte apoptosis and increased ratio of Bax/Bcl-2 at the protein level. Meanwhile, DCM caused slightly myocardial fibrosis with elevated mRNA levels of collagen I and collagen III. Also, DCM resulted in a reduction of mitochondrial DNA (mtDNA) replication and transcription, together with reduced mtDNA content and impaired mitochondrial ultrastructure. All of these changes could be abolished by exercise training. Furthermore, DCM-associated inhibition of PGC-1α and Akt signaling was significantly activated by exercise, indicating that exercise-induced activation of PGC-1α and Akt signaling might be responsible for mediating cardioprotective effect of exercise in DCM.
Exercise preserves cardiac function, prevents myocardial apoptosis and fibrosis, and improves mitochondrial biogenesis in the late stage of DCM. Exercise-induced activation of PGC-1α and Akt signaling might be promising therapeutic targets for advanced DCM.
背景/目的：糖尿病性心肌病（DCM）是糖尿病患者发病和死亡的主要原因。据报道，运动对于在DCM发展过程中保护心脏免受心脏损伤有效。然而，运动在晚期DCM中的潜在心脏保护作用仍不清楚。
7周龄雄性C57BL/6野生型或db/db小鼠，一组进行为期15周的跑步运动训练，另一组保持 sedentary状态。检测心脏功能、心肌细胞凋亡和纤维化以及线粒体生物发生情况，以评估心脏损伤。
运动训练显著逆转了db/db小鼠射血分数和缩短分数的降低。DCM在蛋白质水平上诱导了显著的心肌细胞凋亡并增加了Bax/Bcl-2的比例。同时，DCM导致轻微的心肌纤维化，I型和III型胶原蛋白的mRNA水平升高。此外，DCM导致线粒体DNA（mtDNA）复制和转录减少，同时mtDNA含量降低和线粒体超微结构受损。所有这些变化都可以通过运动训练消除。此外，运动显著激活了与DCM相关的对PGC-1α和Akt信号通路的抑制，表明运动诱导的PGC-1α和Akt信号通路激活可能是运动在DCM中介导心脏保护作用的原因。
运动可维持晚期DCM的心脏功能，预防心肌细胞凋亡和纤维化，并改善线粒体生物发生。运动诱导的PGC-1α和Akt信号通路激活可能是晚期DCM有前景的治疗靶点。
