文章基本信息

标题：Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial K_ATP Channel
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作者：Jie Hao ; Wei-Wei Li ; Hong Du 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2016
卷号：64
期号：6
页码：548-557
DOI：10.1248/cpb.c15-00693
出版社：The Pharmaceutical Society of Japan
摘要：How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen–glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial K_ATP (mitoK_ATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca²⁺ overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoK_ATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.