Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Neuroscience. 2022 Nov 1;503:95-106. doi: 10.1016/j.neuroscience.2022.08.024. Epub 2022 Sep 5.
MicroRNAs (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 indicators, 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.
微小 RNA（miRNAs）被广泛认为在脑血管疾病中发挥独特作用。本研究通过大脑中动脉阻塞（MCAO）模型探讨了微小 RNA 在缺血性中风中的功能。通过生物信息学分析鉴定了大鼠脑中 4 个差异表达的微小 RNA，qRT-PCR 显示 miR-423-5p 在大鼠脑缺血/再灌注损伤中表达最高，在 24 小时达到峰值。在 MCAO 大鼠模型中给予微小 RNA 抑制剂和模拟物后，检测神经评分和脑水含量，并进行氯化三苯基四氮唑（TTC）、苏木精和伊红（H&E）和尼氏染色，以探讨 miR-423-5p 对缺血性中风的影响。随后，应用 Western blot、ELISA、MPO、TUNEL 和商业试剂盒评估 miR-423-5p 对缺血半影组织中 NLRP3 炎性小体、细胞凋亡和氧化应激水平的影响。结果表明，miR-423-5p 敲低可有效改善神经学指标，如脑梗死体积、脑水含量、神经评分和神经组织损伤，并抑制 NLRP3 炎性小体、细胞凋亡和氧化应激。相反，miR-423-5p 模拟物则产生相反的结果。综上所述，抑制 miR-423-5p 的表达可有效减轻缺血性中风，可能成为中风治疗的一个有前途的靶点。
