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微小 RNA-223 靶向 NLRP3 以缓解炎症并减轻脊髓损伤。

MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury.

机构信息

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China; Department of Orthopaedics, Ankang Central Hospital of Shaanxi, No.85 Jinzhou South Road, AnKang 725000, Shaanxi, China.

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China.

出版信息

Life Sci. 2020 Aug 1;254:117796. doi: 10.1016/j.lfs.2020.117796. Epub 2020 May 14.

Abstract

AIMS

To explore the possible mechanism that microRNA-223 regulates the spinal cord injury as well as the posttranscriptional control of genes after spinal injury.

MATERIALS AND METHODS

Rats contusion spinal cord injury model and microglia model were established and examined by pathological test and the inflammatory cytokines levels were evaluated by RT-PCR. Then microRNA-223 was overexpressed in spinal cord to see the impact on rats with spinal cord injury. The overexpression of microRNA-223 in microglia stimulated by LPS was used to assess the inflammation. Then bioinformatic method combined with luciferase reporter genes were used to detect the target gene of microRNA-223. Then NLRP3, one of the target genes of microRNA-223 were regulated to see the impact on microglia as well as spinal injury rats.

KEY FINDINGS

It showed that microRNA-223 increased after acute spinal injury. However, the suppression of microRNA-223 aggravated the spinal injury as well as the inflammation while the over-expression of microRNA-223 alleviated the spinal injury to some extent, decreased the inflammation and improved nervous system function. In vitro, it was found that the over-expression of microRNA-223 in microglia suppressed inflammation induced by LPS and vice versa. NLRP3 was found the target of microRNA-223. The up-regulation of NLRP3 could diminish the effects of microRNA-223 and aggravated inflammation in microglia.

SIGNIFICANCE

The over-expression of microRNA-223 alleviated the inflammation and improved neuron function. NLRP3 was the downstream target of microRNA-223, the overexpression of which led to severe inflammation in microglia.

摘要

目的

探讨 microRNA-223 调控脊髓损伤以及脊髓损伤后基因转录后调控的可能机制。

材料和方法

建立大鼠挫伤性脊髓损伤模型和小胶质细胞模型,通过病理检查进行评估,并通过 RT-PCR 检测炎症细胞因子水平。然后在脊髓中过表达 microRNA-223,观察其对脊髓损伤大鼠的影响。用 LPS 刺激小胶质细胞过表达 microRNA-223,评估其炎症反应。然后采用生物信息学方法结合荧光素酶报告基因检测 microRNA-223 的靶基因。然后调控 microRNA-223 的靶基因 NLRP3,观察其对小胶质细胞和脊髓损伤大鼠的影响。

主要发现

急性脊髓损伤后 microRNA-223 增加。然而,抑制 microRNA-223 加重了脊髓损伤和炎症反应,而过表达 microRNA-223 在一定程度上减轻了脊髓损伤,减轻了炎症反应,改善了神经系统功能。体外实验发现,microRNA-223 在小胶质细胞中的过表达抑制了 LPS 诱导的炎症反应,反之亦然。NLRP3 是 microRNA-223 的靶基因。NLRP3 的上调可以减弱 microRNA-223 的作用,并加重小胶质细胞中的炎症反应。

意义

microRNA-223 的过表达减轻了炎症反应,改善了神经元功能。NLRP3 是 microRNA-223 的下游靶基因,其过表达导致小胶质细胞中严重的炎症反应。

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