Yu Shi-Jia, Yu Ming-Jun, Bu Zhong-Qi, He Ping-Ping, Feng Juan
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2021 Jun;16(6):1024-1030. doi: 10.4103/1673-5374.300455.
Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury. MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury. However, whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood. In this study, we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo. Our results showed that after ischemia/reperfusion injury, miR-670 expression was obviously increased. After miR-670 expression was inhibited with an miR-670 antagomir, cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced. When miR-670 overexpression was induced by an miR-670 agomir, neuronal apoptosis was increased. In addition, we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits. Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury. These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway, which may be a potential target for treatment of cerebral ischemia/reperfusion injury. The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27, 2017 (IRB No. 2017PS035K).
细胞凋亡是一种重要的程序性细胞死亡过程，参与缺血/再灌注损伤。微小RNA被认为在大脑缺血和再灌注损伤调控的分子机制中发挥重要作用。然而，miR-670是否能调节脑缺血/再灌注中的细胞生长和死亡及其潜在机制尚不清楚。在本研究中，我们建立了短暂性大脑中动脉闭塞小鼠模型以及氧糖剥夺和复氧的Neuro 2a细胞模型，以研究miR-670在体外和体内脑缺血/再灌注损伤过程中发挥作用的潜在分子机制。我们的结果显示，缺血/再灌注损伤后，miR-670表达明显增加。用miR-670拮抗剂抑制miR-670表达后，脑缺血/再灌注损伤诱导的神经元死亡明显减少。当用miR-670激动剂诱导miR-670过表达时，神经元凋亡增加。此外，我们还发现miR-670可通过磷酸化促进Yes相关蛋白（Yap）降解，并加重神经元凋亡和神经功能缺损。抑制miR-670可减轻脑缺血/再灌注损伤后的神经功能障碍。这些结果表明，微小RNA-670通过Yap途径加重脑缺血/再灌注损伤，这可能是治疗脑缺血/再灌注损伤的一个潜在靶点。本研究于2017年2月27日获得中国医科大学实验动物管理与使用委员会批准（伦理审查委员会编号：2017PS035K）。
