Background: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.



中文翻译：

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LncRNA SNHG4 在脑缺血再灌注损伤期间通过海绵化 miR-449c-5p 和上调小胶质细胞中的 STAT6 来减轻炎症反应

背景：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lncRNA SNHG4在调节脑缺血再灌注过程中小胶质细胞炎症反应中的作用。
材料和方法：从急性脑梗塞 (ACI) 患者和健康对照者收集血液样本和脑脊液样本。用大鼠构建大脑中动脉闭塞（MCAO）模型。分别应用LPS诱导和氧-葡萄糖剥夺方法在体外模拟小胶质细胞的活化。采用qRT-PCR检测SNHG4、miR-449c-5p及相关炎症因子在体内外的表达。检测了受SNHG4和miR-449c-5p不同表达影响的小胶质细胞的炎症反应。进行荧光素酶测定以验证涉及 SNHG4、miR-449c-5p 和 STAT6 的串扰。
结果：与对照组相比，ACI患者样本和MCAO组小胶质细胞来源的SNHG4表达显着下调，而miR-449c-5p的表达显着上调。SNHG4的过表达和miR-449c-5p的敲低可以抑制小胶质细胞中促炎细胞因子的表达，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 的过表达具有相反的效果。荧光素酶测定证实 SNHG4 可以靶向 miR-449c-5p，而 miR-449c-5p 可以靶向 STAT6。
结论： SNHG4在脑缺血再灌注损伤过程中通过吸附小胶质细胞中的miR-449c-5p来调节STAT6并抑制炎症。