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miR-7-5p 通过降解 sirt1 mRNA 促进脑缺血再灌注损伤。

MiR-7-5p Enhances Cerebral Ischemia-Reperfusion Injury by Degrading sirt1 mRNA.

机构信息

Department of Neurology, The 4th Hospital Affiliated Jiangsu University, Zhenjiang City China; and.

Department of Neurology, Penglai Traditional Medicine Hospital, Penglai City, China.

出版信息

J Cardiovasc Pharmacol. 2020 Aug;76(2):227-236. doi: 10.1097/FJC.0000000000000852.

DOI:10.1097/FJC.0000000000000852
PMID:32453073
Abstract

Cerebral ischemia-reperfusion (I/R) is a kind of neurovascular disease that causes serious cerebral damage. MicroRNAs (miRNAs) have been widely reported to participate in multiple diseases, including cerebral I/R injury. However, the exact mechanisms of miR-7-5p in cerebral I/R injury was not fully elucidated. In this study, we explored the biological role and regulatory mechanism of miR-7-5p in cerebral I/R injury. We established an in vivo model of cerebral I/R by middle cerebral artery occlusion and an in vitro cellular model of cerebral I/R injury through treating neurons (SH-SY5Y cells) with oxygen-glucose deprivation (OGD). In addition, miR-7-5p expression was confirmed to be upregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Moreover, miR-7-5p inhibition overtly suppressed cerebral injury, cerebral inflammation, and SH-SY5Y cells apoptosis. Sirtuin 1 (sirt1) is previously reported to alleviate I/R, and in this study, it was identified to be a target of miR-7-5p based on luciferase reporter assay. Reverse transcription-quantitative polymerase chain reaction revealed sirt1 expression was downregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Besides, miR-7-5p negatively regulated sirt1. Finally, rescue assays delineated sirt1 overexpression recovered the miR-7-5p upregulation-induced promotion on cerebral I/R injury. In conclusion, miR-7-5p enhanced cerebral I/R injury by degrading sirt1, providing a new paradigm to investigate cerebral I/R injury.

摘要

脑缺血再灌注(I/R)是一种引起严重脑损伤的神经血管疾病。microRNAs(miRNAs)已被广泛报道参与多种疾病,包括脑 I/R 损伤。然而,miR-7-5p 在脑 I/R 损伤中的确切机制尚未完全阐明。在这项研究中,我们探讨了 miR-7-5p 在脑 I/R 损伤中的生物学作用和调控机制。我们通过大脑中动脉闭塞建立了体内脑 I/R 模型,通过氧葡萄糖剥夺(OGD)处理神经元(SH-SY5Y 细胞)建立了体外脑 I/R 损伤细胞模型。此外,miR-7-5p 的表达在脑 I/R 大鼠模型和 OGD/R 处理的 SH-SY5Y 细胞中被证实上调。此外,miR-7-5p 抑制明显抑制脑损伤、脑炎症和 SH-SY5Y 细胞凋亡。先前的研究表明 Sirtuin 1(sirt1)可以减轻 I/R,在本研究中,基于荧光素酶报告基因检测,发现 sirt1 是 miR-7-5p 的靶标。逆转录定量聚合酶链反应显示 sirt1 在脑 I/R 大鼠模型和 OGD/R 处理的 SH-SY5Y 细胞中表达下调。此外,miR-7-5p 负调控 sirt1。最后,挽救实验表明 sirt1 的过表达恢复了 miR-7-5p 上调对脑 I/R 损伤的促进作用。总之,miR-7-5p 通过降解 sirt1 增强脑 I/R 损伤,为研究脑 I/R 损伤提供了一个新的范例。

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