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

Diazoxide Protects against Myocardial Ischemia/Reperfusion Injury by Moderating ERS via Regulation of the miR-10a/IRE1 Pathway
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二氮嗪通过调节 miR-10a/IRE1 通路来调节 ERS,从而预防心肌缺血/再灌注损伤

DOI:
10.1155/2020/4957238
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发表时间:
2020-09
影响因子:
--
通讯作者:
Tian Yu
Tian Yu
中科院分区:
生物学2区
文献类型:
--
作者:
Lin Zhang;Shuang Cai;Song Cao;Jia Nie;Wenjing Zhou;Yu Zhang;Ke Li;Haiying Wang;Shouyang Yu;Tian Yu

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目前,再灌注仍是治疗缺血性心脏病最有效的方法。然而,心脏再灌注治疗会导致再灌注损伤,这可能是由于再灌注过程中的内质网应激(ERS)所致。二氮嗪(DZ)是一种高度选择性的线粒体三磷酸腺苷敏感性钾通道开放剂。它对I/R损伤的保护作用已在许多器官如心脏和脑中得到证实。然而,其保护作用的机制尚未完全阐明。microRNAs(miRNAs)广泛参与心脏病的病理过程。在本研究中,我们发现miR-10a的表达在心肌I/R组中高度上调,并且DZ治疗显著降低miR-10a的表达。更重要的是,我们发现DZ治疗可以通过调节I/R和H/R模型中的miR-10a/IRE 1通路来减轻ERS,从而保护心肌H/R损伤。
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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