Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 11;14:3683-3695. doi: 10.2147/DDDT.S245445. eCollection 2020.
Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion.
Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6.
Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6.
SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.
小胶质细胞介导的炎症反应在脑缺血再灌注损伤中起关键作用。本研究旨在探讨长链非编码 RNA SNHG4 在调节脑缺血再灌注期间小胶质细胞炎症反应中的作用。
采集急性脑梗死（ACI）患者和健康对照者的血液样本和脑脊液样本。采用大鼠构建大脑中动脉闭塞（MCAO）模型。分别用 LPS 诱导和氧葡萄糖剥夺方法模拟体外小胶质细胞的激活。qRT-PCR 用于检测体内和体外 SNHG4、miR-449c-5p 和相关炎症因子的表达。检测 SNHG4 和 miR-449c-5p 表达变化后小胶质细胞的炎症反应。通过荧光素酶实验验证 SNHG4、miR-449c-5p 和 STAT6 之间的相互作用。
与对照组相比，ACI 患者样本和 MCAO 组小胶质细胞中的 SNHG4 表达显著下调，而 miR-449c-5p 表达显著上调。SNHG4 过表达和 miR-449c-5p 敲低可抑制小胶质细胞中促炎细胞因子的表达，并促进抗炎因子的表达。同时，磷酸化 STAT6 上调，而小胶质细胞中 SNHG4 的敲低和 miR-449c-5p 的过表达则具有相反的作用。荧光素酶实验证实 SNHG4 可以通过吸附 miR-449c-5p 靶向 STAT6，而 miR-449c-5p 可以靶向 STAT6。
在脑缺血再灌注损伤中，SNHG4 可以通过吸附 miR-449c-5p 调节 STAT6 并抑制炎症反应。
