Diazoxide Protects against Myocardial Ischemia/Reperfusion Injury by Moderating ERS via Regulation of the miR-10a/IRE1 Pathway

二氮嗪通过调节 miR-10a/IRE1 通路缓和 ERS,防止心肌缺血/再灌注损伤

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作者:Lin Zhang, Shuang Cai, Song Cao, Jia Nie, Wenjing Zhou, Yu Zhang, Ke Li, Haiying Wang, Shouyang Yu, Tian Yu

Abstract

Nowadays, reperfusion is still the most effective treatment for ischemic heart disease. However, cardiac reperfusion therapy would lead to reperfusion injury, which may have resulted from endoplasmic reticulum stress (ERS) during reperfusion. Diazoxide (DZ) is a highly selective mitochondrial adenosine triphosphate-sensitive potassium channel opener. Its protective effect on I/R injury has been confirmed in many organs such as the heart and brain. However, the mechanism of its protective effect has not been fully elucidated. MicroRNAs (miRNAs) are widely involved in pathologies of heart disease. In this study, we found that miR-10a expression was highly upregulated in the myocardial I/R groups, and DZ treatment significantly reduced the expression of miR-10a. More importantly, we found that DZ treatment can moderate ERS via regulation of the miR-10a/IRE1 pathway in the I/R and H/R models, thereby protecting myocardial H/R injury.

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