Chen Wei, Ma Mei, Song Yinping, Hua Yijie, Jia Hao, Liu Jiankang, Wang Youhua
Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China.
School of Educational Science, Shaanxi University of Technology, Hanzhong, China.
Antioxid Redox Signal. 2024 Feb;40(4-6):209-221. doi: 10.1089/ars.2022.0168. Epub 2023 Jul 21.
Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M Acetylcholine receptor (MAChR), a receptor abundantly present on cardiac parasympathetic nerves, is closely associated with the development of cardiovascular disease. The present study intends to investigate whether exercise can regulate endoplasmic reticulum stress (ERS) and mitophagy through MAChR to resist myocardial ischemia-reperfusion (I/R) injury and to elucidate its mechanism of action. Exercise enhanced parasympathetic nerve function and increased myocardial MAChR protein expression in I/R rats. In addition, it promoted the protein expression of MFN2 and inhibited the expression of Drp1, Chop, PINK1/Parkin, and PERK/eIF2α/ATF4 signaling pathways, effectively reducing mitophagy, ERS, and apoptosis. At the cellular level, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced hypoxia/reoxygenation (H/R)-induced ERS through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with MAChR inhibitors, the levels of ERS and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and ERS levels, and reduced myocardial apoptosis through MAChR, thereby resisting I/R-induced myocardial injury and improving cardiac function. 40, 209-221.
运动引起的心脏适应性变化已被证明可降低心血管疾病风险，而M型乙酰胆碱受体（MAChR）是心脏副交感神经上大量存在的一种受体，与心血管疾病的发生密切相关。本研究旨在探讨运动是否能通过MAChR调节内质网应激（ERS）和线粒体自噬，以抵抗心肌缺血再灌注（I/R）损伤并阐明其作用机制。运动增强了I/R大鼠的副交感神经功能并增加了心肌MAChR蛋白表达。此外，它促进了MFN2的蛋白表达并抑制了Drp1、Chop、PINK1/Parkin和PERK/eIF2α/ATF4信号通路的表达，有效减少了线粒体自噬、ERS和细胞凋亡。在细胞水平上，5-氨基咪唑-4-甲酰胺核苷酸（AICAR）通过下调H9C2心肌细胞中PERK/eIF2α/ATF4通路蛋白的表达，减少了缺氧/复氧（H/R）诱导的ERS。当用MAChR抑制剂干预时，H/R细胞中ERS水平和PERK/eIF2α/ATF4通路的磷酸化水平升高。运动干预激活了大鼠的副交感神经状态。它通过MAChR抑制心肌线粒体自噬和ERS水平，并减少心肌细胞凋亡，从而抵抗I/R诱导的心肌损伤并改善心脏功能。40, 209 - 221。
