Wang Li, Tu Wenzhan, Li Xuqing, Li Caiyan, Lu Junhong, Dai Peng, Chen Yuewei, Gu Meilin, Li Ming, Jiang Songhe, Yang Guanhu, Li Shengcun
Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Life Sci. 2023 Nov 1;332:122041. doi: 10.1016/j.lfs.2023.122041. Epub 2023 Aug 30.
Stroke can induce cardiac dysfunction without a primary cardiac disease. Exercise can promote the overall rehabilitation of stroke patients and be beneficial for all kinds of heart diseases. However, the mechanisms underlying the protective effects of exercise in stroke-induced cardiac dysfunction are poorly understood. Hence, we aimed to distinguish the different effects of acute and long-term exercise and further study the mechanism of protection against cardiomyopathy caused by stroke. Mice underwent a single acute session or long-term exercise for 30 days, followed by middle cerebral artery occlusion surgery. The expression of apoptosis-related proteins and proinflammatory factors in the heart was evaluated. Then, overexpression of apelin peptide jejunum (APJ) transfected adeno-associated virus type 9 (AAV9) and inhibition of signal transducer and activator of transcription 3 (STAT3) by Stattic were used in stroke mice or hypoxic cardiomyocytes. ML221 were used to inhibit APJ activity in exercise mouse. Thereafter, changes in apoptotic and proinflammatory factors were evaluated. The results demonstrated that chronic exercise prevented myocardial inflammation, apoptosis and cardiac dysfunction after stroke. However, acute exercise did not have similar effects. Exercise maintained the levels of APJ expression and decreased phosphorylated-STAT3 (p-STAT3) activation to protect cardiomyocytes. Moreover, APJ overexpression promoted cardiomyocyte survival and reduced p-STAT3 levels. STAT3 inhibition also reduced apoptosis and proinflammatory factors in mice hearts. Conversely, the protective effect of exercise was eliminated by APJ inhibition. This study showed that exercise can maintain APJ expression and inhibit p-STAT3, thus, conferring protection against myocardial inflammation and apoptosis induced by stroke.
中风可在无原发性心脏病的情况下诱发心脏功能障碍。运动可促进中风患者的全面康复，并对各种心脏病有益。然而，运动对中风诱发的心脏功能障碍的保护作用机制尚不清楚。因此，我们旨在区分急性运动和长期运动的不同效果，并进一步研究预防中风所致心肌病的保护机制。小鼠进行单次急性运动或为期30天的长期运动，随后进行大脑中动脉闭塞手术。评估心脏中凋亡相关蛋白和促炎因子的表达。然后，在中风小鼠或缺氧心肌细胞中使用过表达apelin肽空肠（APJ）的9型腺相关病毒（AAV9）转染以及用Stattic抑制信号转导和转录激活因子3（STAT3）。ML221用于抑制运动小鼠的APJ活性。此后，评估凋亡和促炎因子的变化。结果表明，长期运动可预防中风后的心肌炎症、凋亡和心脏功能障碍。然而，急性运动没有类似效果。运动维持APJ表达水平并降低磷酸化STAT3（p-STAT3）的激活，以保护心肌细胞。此外，APJ过表达促进心肌细胞存活并降低p-STAT3水平。抑制STAT3也可降低小鼠心脏中的凋亡和促炎因子。相反，APJ抑制消除了运动的保护作用。本研究表明，运动可维持APJ表达并抑制p-STAT3，从而对中风诱导的心肌炎症和凋亡起到保护作用。
