Xiang Pu, Hu Jian, Wang Hong, Luo Ying, Gu Chao, Tan Xiaodan, Tu Yujun, Guo Wenjia, Chen Lin, Gao Lin, Chen Rongchun, Yang Junqing
Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
Department of Pharmacy, Dianjiang People's Hospital of Chongqing, Chongqing, 408300, China.
Cell Death Discov. 2022 Feb 28;8(1):89. doi: 10.1038/s41420-022-00885-x.
Studies have reported that miR-204-5p is involved in multiple biological processes. However, little is known about the expression and mechanism of miR-204-5p in cerebral ischemia and reperfusion injury. This study found that miR-204-5p expression was significantly downregulated in the blood of patients with ischemic stroke, MCAO/R rat brains, and OGD/R neurons. Overexpression of miR-204-5p markedly reduced infarct volume and neurological impairment and alleviated the inflammatory response in vivo. miR-204-5p promoted neuronal viability and reduced apoptotic cells in vitro. Mechanically, miR-204-5p was negatively regulated by the expression lncRNA TUG1 upstream and down-regulated COX2 expression downstream. Therefore, the TUG1/miR-204-5p/COX2 axis was involved in ischemia and reperfusion-induced neuronal damage. This finding may provide a novel strategy for the treatment of cerebral ischemia and reperfusion injury.
研究报道称，miR-204-5p参与多种生物学过程。然而，关于miR-204-5p在脑缺血再灌注损伤中的表达及机制知之甚少。本研究发现，在缺血性中风患者血液、大脑中动脉闭塞/再灌注（MCAO/R）大鼠脑以及氧糖剥夺/再灌注（OGD/R）神经元中，miR-204-5p表达显著下调。在体内，miR-204-5p过表达显著减小梗死体积、减轻神经功能缺损并减轻炎症反应。在体外，miR-204-5p促进神经元活力并减少凋亡细胞。机制上，lncRNA TUG1在miR-204-5p上游对其表达进行负调控，而miR-204-5p在下游下调COX2表达。因此，TUG1/miR-204-5p/COX2轴参与了缺血再灌注诱导的神经元损伤。这一发现可能为脑缺血再灌注损伤的治疗提供新策略。
