miR-146a在大鼠神经病理性疼痛模型中的表达及其作用机制

基础医学与临床 ›› 2015, Vol. 35 ›› Issue (7): 911-915.

miR-146a在大鼠神经病理性疼痛模型中的表达及其作用机制

王之遥¹,申乐²,赵欣¹,黄宇光³

1. 中国医学科学院北京协和医学院北京协和医院麻醉科
2. 中国医学科学院北京协和医院
3. 北京协和医院

收稿日期:2015-03-20 修回日期:2015-05-18 出版日期:2015-07-05 发布日期:2015-06-23
通讯作者: 黄宇光 E-mail:garybeijing@163.com
基金资助:
神经病理性疼痛相关微小RNA 在中枢感觉神经传导通路中的功能研究;miR-203活化的JAK-STAT信号通路传导对神经病理性疼痛机制及干预的研究

Expression level and mechanism of miRNA-146a in neuropathic pain rat

Received:2015-03-20 Revised:2015-05-18 Online:2015-07-05 Published:2015-06-23

摘要/Abstract

摘要： 目的研究miR-146a对神经病理性疼痛的调控机制。方法将大鼠随机分为：1)Na?ve组(n=12)；2)假手术组(n=12)：进行大鼠双侧假手术；3)双侧慢性压迫损伤（bCCI）组(n=12)：建立大鼠双侧坐骨神经结扎模型。在建模前1d及后第3、7和14d监测机械刺激诱发痛、热刺激诱发痛行为学指标；实时定量PCR法检测背根神经节（L4-L6）miR146-a及TNF-α受体相关因子6（TRAF6）、白介素1受体相关激酶（IRAK1）的mRNA表达水平；Western blot法检测TRAF6及IRAK1蛋白表达。结果 bCCI大鼠双足热刺激诱发痛痛阈、机械刺激诱发痛痛阈较Na?ve组、假手术组显著降低(p<0.05)。术后第14d bCCI组miR-146a表达水平较Na?ve组显著下降(p<0.05)。bCCI组TRAF6、IRAK1的mRNA表达水平较Na?ve组升高(p<0.05)；TRAF6、IRAK1蛋白表达水平较假手术组和Na?ve组均显著增加(p<0.05)。结论神经病理性疼痛大鼠背根神经节miR-146a表达水平下调，miR-146a可能通过过度激活其靶基因TRAF6和IRAK1发挥作用。

关键词: 神经病理性疼痛, miRNA-146a, IRAK1, TRAF6

Abstract: Objective To evaluate the expression level of miRNA-146a (miR-146a) in neuropathic pain of bilateral chronic constriction injury (bCCI) rat and the effect of miR-146a on its target gene IRAK1 and TRAF6, and to explore the regulatory mechanism of miR-146a in neuropathic pain. Methods 36 female rats were divided randomly into bCCI group in which 12 rats received bilateral chronic constriction surgery, sham group and na?ve group. Behavior test were performed on the day before surgery and on day 3,7 and 14 after surgery. L4-L6 dorsal root ganglions were harvested on day 14 after surgery. RT-qPCR was used to test the mRNA expression of miR-146a, IRAK1 and TRAF6. Western Blot was performed to explore the protein expression of IRAK1 and TRAF6. Results Pain-related behavioral test scores of bCCI rats were significantly decreased as compared to sham group and na?ve group rats at each time point after surgery (P<0.05). Compared with sham group and na?ve group, the expression of miRNA-146a was greatly decreased, whereas IRAK1 mRNA and TRAF6 mRNA were significant increased on day 14 after surgery in bCCI rat group. Western Blot result showed that IRAK1 and TRAF6 on protein level increased in DRG of bCCI rat on day 14 postoperatively (P<0.05). Conclusion Our research suggested that decreased expression of miR-146a in DRG of bCCI rats and miR-146a might contribute to neuropathic pain by up-regulating IRAK1 and TRAF6.

Key words: neuropathic pain, miR-146a, IRAK1, TRAF6

中图分类号:

R 164

王之遥申乐赵欣黄宇光. miR-146a在大鼠神经病理性疼痛模型中的表达及其作用机制[J]. 基础医学与临床, 2015, 35(7): 911-915.

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