Effect of miR-19a on neuropathic pain in chronic constriction injury rats and its mechanism

Bing LIANG; Tieli DONG

doi:10.16016/j.1000-5404.201711033

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Effect of miR-19a on neuropathic pain in chronic constriction injury rats and its mechanism

Basic Medicine | 更新时间：2026-01-09

- Effect of miR-19a on neuropathic pain in chronic constriction injury rats and its mechanism
- Journal of Third Military Medical University Vol. 40, Issue 7, Pages: 590-595(2018)
- 作者机构：
  
  1.450099 郑州，河南中医药大学第一附属医院麻醉科
  2.450014 郑州，郑州大学第二附属医院麻醉科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201711033
  CLC： R362.21;R394.3;R441.1
- Received：06 November 2017，
  
  Revised：2017-12-15，
  
  Published：15 April 2018
- 稿件说明：
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Bing LIANG, Tieli DONG. Effect of miR-19a on neuropathic pain in chronic constriction injury rats and its mechanism[J]. Journal of Third Military Medical University, 2018, 40(7): 590-595.
DOI：

Bing LIANG, Tieli DONG. Effect of miR-19a on neuropathic pain in chronic constriction injury rats and its mechanism[J]. Journal of Third Military Medical University, 2018, 40(7): 590-595. DOI： 10.16016/j.1000-5404.201711033.

摘要

目的

观察miR-19a对慢性压迫性损伤(chronic constriction injury，CCI)大鼠神经病理性疼痛的作用，并探讨其潜在机制。

方法

75只雄性SD大鼠按随机数字表法分为3组：假手术组，行假手术；CCI组，坐骨神经结扎法构建CCI大鼠模型；CCI+ inhibitor组，CCI大鼠鞘内注射miR-19a inhibitor。于术前当天(0 d)和术后3、7、14、21 d观察机械缩足反射阈值(mechanical withdrawal threshold，MWT)和热刺激反射潜伏期(thermal withdrawal latency，TWL)的变化。采用RT-qPCR检测腰椎脊髓中促炎因子IL-6、TNF-α、IL-1β mRNA及JAK2和STAT3表达的变化，Western blot检测SOCS3蛋白水平的表达，荧光素酶报告基因技术验证miR-19a的靶基因。

结果

与假手术组比较，CCI组大鼠脊髓的miR-19a表达显著上升(

0.05)，MWT显著降低，TWL显著缩短(

0.05)。与CCI组比较，CCI+inhibitor组MWT显著升高，TWL显著延长(

0.05)。RT-qPCR检测结果表明，CCI可显著促进促炎因子IL-6、TNF-α、IL-1β mRNA的表达；而与CCI组比较，CCI+inhibitor组IL-6、TNF-α、IL-1β mRNA表达水平均显著降低(

0.05)。另一方面，与假手术组比较，CCI组大鼠术后脊髓中JAK2和STAT3 mRNA水平明显增加；与CCI组比较，CCI+inhibitor组术后脊髓中JAK2和STAT3的表达显著降低(

0.01)。荧光素酶报告基因检测结果表明JAK2/STAT3上游的负调控因子SOCS3是miR-19a的靶基因。Western blot检测结果表明CCI组大鼠脊髓中SOCS3水平较假手术组升高，且SOCS3水平在CCI术后第7天达到最高，而后呈下降趋势；与CCI组比较，CCI+ inhibitor组SOCS3表达明显上升(

0.05)。

结论

miR-19a inhibitor能缓解CCI大鼠机械性触诱发痛和热痛觉过敏，该作用与SOCS3介导的JAK2/STAT3通路有关。

Abstract

Objective

To determine the effect of miR-19a on neuropathic pain in rats and investigate the potential mechanisms.

Methods

A rat model of chronic constriction injury (CCI) was established by sciatic nerve ligation. A total of 75 male SD rats were randomly divided into 3 groups

that is

sham group

CCI group

CCI+inhibitor group (intrathecal injection of miR-19a inhibitor). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of each group were observed on the surgery day (regarded as 0 d) and 3

14 and 21 d post-operatively. Simultaneously

the mRNA expression levels of IL-6

TNF-α

IL-1β

JAK2 and STAT3 in the lumbar spinal cord were detected with RT-qPCR. Then

luciferase report gene assay was used to verify the target genes of miR-19a.

Results

Compared to the sham group

miR-19a was highly expressed in the spinal cord tissue of CCI group (

0.05)

while MWT and TWL were significantly decreased (

0.05). However

MWT and TWL were markedly increased in the CCI+inhibitor group when compared with the CCI group (

0.05). What is more

RT-qPCR analysis showed that compared with the sham group

the pro-inflammatory factors

such as IL-6

TNF-α and IL-1β were highly increased in the CCI group

while they were decreased in the CCI+inhibitor group. Compared with the sham group

the mRNA expression levels of JAK2 and STAT3 were significantly enhanced in the spinal cord tissues of CCI rats

while inhibition of miR-19a reversed these effects (

0.05). Further luciferase assay identified that SOCS3

an upstream suppressor of JAK2/STAT3

was a target gene of miR-19a. Western blot assay showed the level of SOCS3 was highly expressed in the CCI group when compared with sham group

and it reached the highest at day 7 post-operatively. Compared with CCI group

the SOCS3 expression was markedly increased in CCI+inhibitor group (

0.05).

Conclusion

miR-19a inhibitor alleviates the mechanical withdrawal pain and thermal hyperalgesia

and this function is associated with SOCS3-mediated JAK2/STAT3 pathway.

关键词

Keywords

references

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