Department of Neurosurgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; and.
Department of Surgical Intensive Care Unit, Children's Hospital of Nanjing Medical University, Nanjing, China.
J Cardiovasc Pharmacol. 2020 Nov;76(5):627-634. doi: 10.1097/FJC.0000000000000898.
Cerebral ischemia-reperfusion (I/R) injury is a terrible disease which results in the dysfunction and structural damage of brain tissues. Growing evidence implies that miR-455-5p is implicated in the regulation of pathogenesis of several diseases. The aim of this study is to reveal the role of miR-455-5p in cerebral I/R injury and the regulatory mechanism. We established a vitro model by inducing SH-SY5Y and PC-12 cells with oxygen-glucose deprivation and reoxygenation. The experimental cerebral I/R rat model was established by middle cerebral artery occlusion operation. The findings indicated that miR-455-5p expression was downregulated in oxygen-glucose deprivation and reoxygenation induced cells and I/R rat model. In addition, miR-455-5p upregulation inhibited SH-SY5Y cell apoptosis and cerebral damage, whereas miR-455-5p silencing promoted SH-SY5Y cell apoptosis and cerebral damage. Mechanistically, luciferase reporter assay corroborated that miR-455-5p could bind with feline mcDonough sarcoma-like tyrosine kinase 3 (FLT3) mRNA. However, the role of FLT3 in cerebral I/R injury was rarely investigated. Real-time polymerase chain reaction revealed that FTL3 expression was negatively regulated by miR-455-5p. FTL3 upregulation reversed the inhibitory effects of miR-455-5p upregulation on PC-12 and SH-SY5Y cell apoptosis. Therefore, our study verified that miR-455-5p improved cerebral I/R injury by targeting FLT3, which suggests a potential new target for the prevention of cerebral I/R injury.
脑缺血再灌注（I/R）损伤是一种导致脑组织功能障碍和结构损伤的严重疾病。越来越多的证据表明，miR-455-5p 参与了几种疾病的发病机制的调节。本研究旨在揭示 miR-455-5p 在脑 I/R 损伤中的作用及其调控机制。我们通过诱导 SH-SY5Y 和 PC-12 细胞氧葡萄糖剥夺和再氧合建立体外模型。通过大脑中动脉闭塞手术建立实验性脑 I/R 大鼠模型。研究结果表明，miR-455-5p 在氧葡萄糖剥夺和再氧合诱导的细胞和 I/R 大鼠模型中的表达下调。此外，miR-455-5p 的上调抑制了 SH-SY5Y 细胞凋亡和脑损伤，而 miR-455-5p 的沉默则促进了 SH-SY5Y 细胞凋亡和脑损伤。机制上，荧光素酶报告基因检测证实 miR-455-5p 可以与猫 McDonough 肉瘤样酪氨酸激酶 3（FLT3）mRNA 结合。然而，FLT3 在脑 I/R 损伤中的作用很少被研究。实时聚合酶链反应显示，FLT3 的表达受 miR-455-5p 的负调控。FLT3 的上调逆转了 miR-455-5p 上调对 PC-12 和 SH-SY5Y 细胞凋亡的抑制作用。因此，我们的研究证实，miR-455-5p 通过靶向 FLT3 改善脑 I/R 损伤，这为预防脑 I/R 损伤提供了一个新的潜在靶点。
