Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, China.
Key Laboratory of Brain Science, Zunyi Medical University, 563000 Zunyi, China.
Oxid Med Cell Longev. 2020 Sep 8;2020:4957238. doi: 10.1155/2020/4957238. eCollection 2020.
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.
如今，再灌注仍然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，这可能是再灌注过程中内质网应激（ERS）引起的。二氮嗪（DZ）是一种高度选择性的线粒体三磷酸腺苷敏感钾通道开放剂。它在心脏和大脑等许多器官的 I/R 损伤中的保护作用已得到证实。然而，其保护作用的机制尚未完全阐明。微小 RNA（miRNA）广泛参与心脏病的病理过程。在这项研究中，我们发现 miR-10a 的表达在心肌 I/R 组中高度上调，DZ 治疗可显著降低 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/IRE1 通路来适度缓解 ERS，从而保护心肌 H/R 损伤。
