Chem Pharm Bull (Tokyo). 2016;64(6):
Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel

The Second Hospital of Hebei Medical University.

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 KATP (mitoKATP) 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 Ca(2+) 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 mitoKATP 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.

Chem Pharm Bull (Tokyo). 2016;
维生素C在激活线粒体KATP通道对缺血/再灌注损伤的心脏保护中的作用

河北医科大学第二医院。

如何提供有效的预防和治疗心肌缺血/再灌注（I / R）损伤和研究I / R损伤的潜在机制是当前研究的热点。这项研究旨在阐明维生素C（VC）对心肌I / R损伤的作用和心脏保护机制。我们的研究引入了两种不同的I / R模型：体外I / R和初级新生大鼠心肌细胞中的氧葡萄糖剥夺/恢复（OGD / R）。我们使用了线粒体通透性转换孔（mPTP）开放剂lonidamine（LND）和线粒体KATP（mitoKATP）通道抑制剂5-羟基癸酸酯（5-HD）来分析其潜在机制。我们发现在我们的模型中，用VC进行的后处理可降低I / R损伤。用VC进行的后处理显着降低了I / R诱导的损伤，减弱了细胞凋亡，并通过缓解Ca（2+）超载，活性氧爆发，抑制mPTP的开放以及防止线粒体，维持了线粒体的功能完整性。膜电位（ΔΨm）去极化。 VC后处理可增加Akt和糖原合酶激酶（GSK）-3β的磷酸化。目前的结果表明，VC可能通过激活mitoKATP通道来抑制mPTP的开放，从而保护心肌免受I / R诱导的损伤。 VC通过激活磷脂酰肌醇3激酶（PI3K）-Akt信号通路来介导心脏保护作用。这些发现可能有助于开发针对I / R损伤的临床心脏保护新策略。

Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel - PubMed
https://pubmed.ncbi.nlm.nih.gov/27250789/