Zhang Jian-Song, Hou Pin-Pin, Shao Shuai, Manaenko Anatol, Xiao Zhi-Peng, Chen Yan, Zhao Bing, Jia Feng, Zhang Xiao-Hua, Mei Qi-Yong, Hu Qin
Central Laboratory, Renji Hospital; Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Central Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Neural Regen Res. 2022 Aug;17(8):1769-1775. doi: 10.4103/1673-5374.332154.
Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1β. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.
神经炎症是导致脑缺血/再灌注后脑损伤发生的主要病理生理因素。缺血性中风后微小RNA（miR）-455-5p的下调被认为是缺血后神经元损伤的潜在生物标志物和治疗靶点。然而，miR-455-5p在缺血/再灌注后炎症反应中的作用及其潜在机制尚未得到评估。在本研究中，通过短暂阻断大脑中动脉1小时后再灌注建立脑缺血/再灌注损伤小鼠模型。在大脑中动脉闭塞（MCAO）前2小时或MCAO后0小时和1小时，将agomir-455-5p、antagomir-455-5p及其阴性对照脑室内注射。结果显示，脑缺血/再灌注降低了脑组织和外周血中miR-455-5p的表达。agomir-455-5p预处理增加了脑组织中miR-455-5p的表达，减少了脑梗死体积，并改善了神经功能。此外，将原代培养的小胶质细胞暴露于氧糖剥夺3小时，然后再复氧21小时以模拟脑缺血/再灌注。miR-455-5p降低了C-C趋化因子受体5型mRNA和蛋白水平，抑制了小胶质细胞活化，并减少了炎症因子肿瘤坏死因子-α和白细胞介素-1β的产生。这些结果表明，miR-455-5p是治疗脑缺血/再灌注损伤的潜在生物标志物和治疗靶点，并且它通过抑制C-C趋化因子受体5型表达和减少神经炎症反应来减轻脑缺血/再灌注损伤。
