Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, PR China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, PR China.
Department of Rehabilitation Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, PR China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, PR China.
Chem Biol Interact. 2022 May 1;358:109900. doi: 10.1016/j.cbi.2022.109900. Epub 2022 Mar 17.
Stroke is a leading cause of death and disability worldwide and the cerebral ischemia/reperfusion (I/R) induced injury is a common phenomenon of stroke. The pathogenesis and effective treatment of I/R-induced brain tissue damage is limited. In this study, the rat model of middle cerebral artery occlusion (MCAO) and the cell model of oxygen and glucose deprivation/reperfusion (OGD/R) were applied to investigate the possible role of the microRNA in ischemic stroke. MCAO/R and OGD/R caused the downregulation of miR-203a-3p and miR-153-3p, the upregulation of SRC. SRC was identified to be a common target for miR-203a-3p and miR-153-3p. Both miR-203a-3p and miR-153-3p inhibited SRC expression at the mRNA and protein levels. miR-203a-3p and miR-153-3p improved the cognitive deficits through targeting SRC. Moreover, miR-203a-3p and miR-153-3p relieved the apoptosis, decreases NLRP3 inflammasome activity, decreases oxidative stress and inflammation in hippocampal neuron through targeting SRC. Moreover, the MAPK signaling pathway was confirmed to be the downstream for miR-203a-3p and miR-153-3p in vivo and in vitro. Thus, miR-203a-3p and miR-153-3p confers neuroprotective effects against ischemic stroke via attenuation of apoptosis, oxidative stress and inflammatory pathways through inhibiting SRC-dependent MAPK signaling pathway in vivo and in vitro, suggesting new therapeutic targets for the prevention and treatment of stroke.
中风是全球范围内导致死亡和残疾的主要原因，而脑缺血/再灌注 (I/R) 诱导的损伤是中风的常见现象。I/R 诱导的脑组织损伤的发病机制和有效治疗方法有限。在这项研究中，应用大脑中动脉闭塞 (MCAO) 大鼠模型和氧葡萄糖剥夺/再灌注 (OGD/R) 细胞模型，研究 microRNA 在缺血性中风中的可能作用。MCAO/R 和 OGD/R 导致 miR-203a-3p 和 miR-153-3p 下调，SRC 上调。SRC 被鉴定为 miR-203a-3p 和 miR-153-3p 的共同靶标。miR-203a-3p 和 miR-153-3p 均在 mRNA 和蛋白水平上抑制 SRC 表达。miR-203a-3p 和 miR-153-3p 通过靶向 SRC 改善认知缺陷。此外，miR-203a-3p 和 miR-153-3p 通过靶向 SRC 减轻海马神经元中的细胞凋亡、降低 NLRP3 炎性小体活性、减少氧化应激和炎症。此外，MAPK 信号通路被证实是体内和体外 miR-203a-3p 和 miR-153-3p 的下游通路。因此，miR-203a-3p 和 miR-153-3p 通过抑制 SRC 依赖性 MAPK 信号通路，在体内和体外减轻细胞凋亡、氧化应激和炎症途径，发挥对缺血性中风的神经保护作用，为中风的预防和治疗提供了新的治疗靶点。
