Inhibition of miR-423-5p Exerts Neuroprotective Effects in an Experimental Rat Model of Cerebral Ischemia/Reperfusion Injury

被引:7
作者
Luo, Jing [1 ,5 ]
Jiang, Ning [1 ,5 ]
Chen, Jialei [2 ]
Yu, Gao [1 ,5 ]
Zhao, Jing [3 ]
Yang, Changhong [1 ,4 ]
Zhao, Yong [1 ,5 ]
机构
[1] Chongqing Med Univ, Dept Pathol, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Dept Otorhinolaryngol, Affiliated Hosp 1, Chongqing, Peoples R China
[3] Chongqing Med Univ, Dept Pathophysiol, Chongqing 400016, Peoples R China
[4] Chongqing Med Univ, Dept Bioinformat, Chongqing 400016, Peoples R China
[5] Chongqing Med Univ, Dept Pathol, Affiliated Hosp 1, Chongqing 400016, Peoples R China
基金
中国国家自然科学基金;
关键词
cerebral I; R injury; miR-423-5p; NLRP3; inflammasome; apoptosis; oxidative stress; NLRP3 INFLAMMASOME ACTIVATION; OXIDATIVE STRESS; REPERFUSION; MECHANISMS; ISCHEMIA; EXPRESSION; STROKE; TARGET; GENE;
D O I
10.1016/j.neuroscience.2022.08.024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
(miRNAs) are widely acknowledged to play a unique role in cerebrovascular disease. This research investigates the function of microRNAs in ischemic stroke via a middle cerebral artery occlusion (MCAO) model. Four differentially expressed microRNAs in rat brains were identified by bioinformatics analysis, and qRT-PCR showed that miR-423-5p exhibited the highest expression in cerebral ischemia/reperfusion injury in rats, with peak levels observed at 24 hours. After microRNA inhibitors and mimics were administrated in the rat model of MCAO, the neurological scores and brain water content were detected, and triphenyltetrazolium chloride (TTC), Hematoxylin and Eosin (H&E), and Nissl staining were conducted to explore the influence of miR-423-5p on ischemic stroke. Subsequently, western blot, ELISA, MPO, TUNEL and commercial assay kits were applied to assess the influence of miR-423-5p on NLRP3 inflammasome, apoptosis, and oxidative stress levels in ischemic penumbra tissue. The results showed that miR-423-5p knockdown could effectively improve neurological indica-tors, such as cerebral infarct volume, brain water content, neurological scores, and nerve tissue damage, and inhibit the NLRP3 inflammasome, apoptosis, and oxidative stress. In contrast, the miR-423-5p mimic yielded opposite results. In conclusion, inhibition of miR-423-5p expression could effectively attenuate ischemic stroke and might be considered a promising target for stroke.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:95 / 106
页数:12
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