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微小 RNA-210 通过抑制 JAK-STAT 通路的炎症反应促进脊髓损伤恢复。

MicroRNA-210 promotes spinal cord injury recovery by inhibiting inflammation via the JAK-STAT pathway.

机构信息

Department of Orthopedic, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6609-6615. doi: 10.26355/eurrev_201810_16135.

Abstract

OBJECTIVE

To investigate the effect of microRNA-210 on the spinal cord injury (SCI) and its underlying mechanism.

MATERIALS AND METHODS

The mouse SCI model was established. Mice were randomly assigned into 4 groups, namely the sham operation group (sham group), surgery group (SCI group), surgery+NC group (SCI+NC group) and surgery+microRNA-210 overexpression group (SCI+microRNA-210 mimics group). The mRNA levels of microRNA-210 and the key genes in the JAK-STAT pathway of the four groups were detected by Real-Time Polymerase Chain Reaction (RT-PCR) at different time points. Protein levels of JAK2 and STAT3 in mice of the four groups were detected by Western blot. To investigate the role of microRNA-210 in SCI recovery, changes in the motor function of mice were detected.

RESULTS

Grip strengths of right and left forelimbs in mice from the sham group were temporarily decreased at the early stage after surgery, which were gradually recovered to the preoperative levels on the 3rd postoperative day. However, mice in SCI group were unable to complete the grip strength determination at the early stage after surgery. Mice in SCI group were capable of grasping on the 7th postoperative day. Besides, grip strengths of mice in SCI group were remarkably lower than those of sham group until the end-point (on the 50th day). Furthermore, mRNA levels of microRNA-210 in mice of SCI group were decreased in a time-dependent manner (p<0.05). Higher grip strengths were observed in mice of SCI+microRNA-210 mimics group in comparison with those of SCI group and SCI+NC group (p<0.05). In addition, Western blot showed that protein levels of JAK2 and STAT3 in mice of SCI group were increased in a time-dependent manner (p<0.05). Moreover, protein levels of JAK2, STAT3, and MCP-1 in mice of SCI+NC group were remarkably higher than those in the sham group and SCI+microRNA-210 mimics group (p<0.05).

CONCLUSIONS

MicroRNA-210 is down-regulated in SCI mice. Grip strengths of SCI mice can be recovered after microRNA-210 overexpression via inhibiting inflammatory response by the JAK-STAT pathway.

摘要

目的

探讨 microRNA-210 对脊髓损伤(SCI)的影响及其机制。

材料和方法

建立小鼠 SCI 模型。将小鼠随机分为 4 组:假手术组(假手术组)、手术组(SCI 组)、手术+NC 组(SCI+NC 组)和手术+microRNA-210 过表达组(SCI+microRNA-210 模拟组)。不同时间点采用实时聚合酶链反应(RT-PCR)检测 4 组小鼠 microRNA-210 及 JAK-STAT 通路关键基因的 mRNA 水平。Western blot 检测 4 组小鼠 JAK2 和 STAT3 蛋白水平。为了探讨 microRNA-210 在 SCI 恢复中的作用,检测了小鼠运动功能的变化。

结果

假手术组小鼠术后早期右、左前肢握力暂时下降,术后第 3 天逐渐恢复术前水平。然而,SCI 组小鼠在术后早期无法完成握力测定。SCI 组小鼠在术后第 7 天能够抓握。此外,SCI 组小鼠的握力一直显著低于假手术组,直到终点(第 50 天)。此外,SCI 组小鼠 microRNA-210 的 mRNA 水平呈时间依赖性下降(p<0.05)。与 SCI 组和 SCI+NC 组相比,SCI+microRNA-210 模拟组小鼠的握力更高(p<0.05)。此外,Western blot 显示 SCI 组小鼠 JAK2 和 STAT3 蛋白水平呈时间依赖性升高(p<0.05)。此外,SCI+NC 组小鼠 JAK2、STAT3 和 MCP-1 蛋白水平明显高于假手术组和 SCI+microRNA-210 模拟组(p<0.05)。

结论

SCI 小鼠中 microRNA-210 下调。过表达 microRNA-210 可通过抑制 JAK-STAT 通路的炎症反应恢复 SCI 小鼠的握力。

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