The mitochondria-targeted antioxidant MitoQ ameliorates myocardial ischemia-reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy in type 2 diabetic rats
The mitochondria-targeted antioxidant MitoQ ameliorates myocardial ischemia-reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy in type 2 diabetic rats
复制标题
线粒体靶向抗氧化剂 MitoQ 通过增强 PINK1/Parkin 介导的线粒体自噬来改善 2 型糖尿病大鼠的心肌缺血再灌注损伤
DOI：
10.1007/s12192-022-01273-1
复制
发表时间：
2022-04-15
影响因子：
3.8
通讯作者：
Xia, Zhongyaun
中科院分区：
文献类型：
--
作者：
Ji, Yelong;Leng, Yan;Xia, Zhongyaun
2型糖尿病心脏更容易受到心肌缺血再灌注(MIR)损伤的影响，这种损伤涉及线粒体吞噬状态降低，机制尚不清楚。MitoQ是一种针对线粒体的抗氧化剂，已被证明通过上调线粒体吞噬功能对缺血再灌注损伤具有保护作用。本研究的目的是探讨在2型糖尿病(T2D)MIR损伤过程中，MitoQ对心肌的影响。在这里，本研究发现PINK1/Parkin下调的2型糖尿病心脏遭受更多的MIR损伤，伴随着线粒体吞噬功能的减少。在活体实验中，给予MitoQ治疗可显著降低CK-MB、LDH、心肌梗死、心肌病理损害和心肌细胞凋亡，改善心功能、细胞有丝分裂状态和PINK1/Parkin通路。此外，MitoQ显著减轻高糖/高脂和缺氧/复氧诱导的H9C2细胞损伤，表现为减少心肌细胞凋亡和ROS产生，增加细胞存活率、线粒体膜电位水平和PINK1/Parkin表达。然而，线粒体分裂抑制物(mdivi-1)，一种丝裂原吞噬的抑制剂，在体外模型中逆转了PINK1/Parkin通路的改善和蛋白表达水平。结论：MIR通过减少线粒体吞噬作用，对T2D细胞造成更严重的损伤。MitoQ可通过PINK1/Parkin通路上调线粒体吞噬功能，对T2D缺血再灌注后的心肌起到保护作用。
Type 2 diabetic hearts are more vulnerable to myocardial ischemia reperfusion (MIR) injury, which involves decreased mitophagy status with unknown mechanisms. MitoQ, a mitochondria-targeted antioxidant, has been shown to have protection against ischemia reperfusion injury through upregulating mitophagy. The aim of this study was to investigate the effects of MitoQ on myocardium during MIR injury in type 2 diabetes (T2D). Herein, this study discovered that type 2 diabetic hearts with PINK1/Parkin downregulation suffered more MIR injury accompanied by reduced mitophagy. Treatment with MitoQ significantly decreased the levels of CK-MB, LDH, myocardial infarction, myocardial pathological damage, and cardiomyocytes apoptosis, while it improved cardiac function, mitophagy status, and PINK1/Parkin pathway in vivo study. Furthermore, MitoQ significantly reduced high glucose/high fat and hypoxia/reoxygenation induced injury in H9C2 cells as evidenced by reduced cardiomyocytes apoptosis and ROS production, and increased cell viability, the level of mitochondrial membrane potential, PINK1/Parkin expression. However, mitochondrial division inhibitor (mdivi-1), an inhibitor of mitophagy, reversed the improvement and protein expression levels of PINK1/Parkin pathway in vitro models. In conclusion, MIR induced more severe damage in T2D by reduction of mitophagy. MitoQ can confer cardioprotection following MIR in T2D by mitophagy up-regulation via PINK1/Parkin pathway.