基础医学与临床 ›› 2016, Vol. 36 ›› Issue (5): 661-665.

• 研究论文 • 上一篇    下一篇

环巴明抑制SHH信号通路缓解大鼠神经病理性疼痛

冯晓雪1,杨晓秋2,刘丹彦1   

  1. 1. 重庆医科大学附属第一医院
    2. 重庆医科大学
  • 收稿日期:2015-10-19 修回日期:2016-03-17 出版日期:2016-05-05 发布日期:2016-04-26
  • 通讯作者: 刘丹彦 E-mail:Liudanyan418@qq.com
  • 基金资助:
    卫生部国家临床重点专科建设项目;重庆市医学重点学科项目;重庆市渝中区科技计划项目

Cyclopamine relieves neuropathic pain of rats by Inhibiting SHH signaling pathway

  • Received:2015-10-19 Revised:2016-03-17 Online:2016-05-05 Published:2016-04-26

摘要: 目的 拟探讨环巴明抑制SHH信号通路对坐骨神经分支选择性损伤(SNI)大鼠的痛敏改变及脊髓水平BDNF、NR2B变化的影响。方法 将大鼠随机分为对照组(control组)、坐骨神经分支选择性损伤组(SNI组)、溶剂对照组(SNI-vehicle组)和环巴明组(SNI-CP组),各组12只。分别于建模前1 d、建模后1和7 d测定机械缩足反应阈(PMWT)。于建模后7 d行为学测量后处死大鼠取L4-6脊髓组织,用Western blot法及实时荧光定量PCR法测定脊髓组织SHH、GLI1及BDNF表达,用免疫组化法测定脊髓组织NR2B蛋白表达。结果 与对照组相比,SNI组、SNI-vehicle组和SNI-CP组PMWT均降低,脊髓组织SHH、GLI1及BDNF蛋白及mRNA表达均上调,且脊髓组织NR2B表达亦上调(P<0.05);但与SNI组相比,SNI-CP组经环巴明处理后PMWT升高,且脊髓组织SHH、GLI1及BDNF表达下调,脊髓组织NR2B表达亦下调(P<0.05)。 结论 环巴明抑制SHH信号通路能改善SNI大鼠神经病理性疼痛,其机制可能与其调节脊髓水平BDNF和NR2B蛋白表达有关。

关键词: 【关键词】:SHH信号通路, 环巴明, 神经病理性疼痛, BDNF, NR2B

Abstract: Objective To explore the effect of inhibiting SHH signaling pathway on the change of hyperalgesia and the change of the BDNF, NR2B level in spinal cord of spared nerve injury rats. Methods Rats were randomly divided into Sham operation group (control group), Spared nerve injury group (SNI group), Solvent group group(SNI-vehicle group) and inhibitor group (SNI-CP group) (n=12). Adopt the method of sciatic nerve branch selective damage to make neuropathic pain models. Pain behavior was assessed and mechanical pain threshold(PMWT) was measured at 1d before operation and the 1, 7 d after SNI operation. After 7 d, animals were then sacrificed and the lumbar segement (L4-6) of the spinal cord was obtained. The expression of SHH, GLI1 and BDNF was detected by Western blotting and Quantitative Real-time PCR method, and the expression of NR2B in the spinal cord was detected by immunohistochemistry method. Results Compared with control group, after the SNI operation in SNI group, SNI-vehicle group and SNI-CP group PMWT was significantly decreased, the protein and mRNA expression of SHH, GLI1 and BDNF were obviously increased, the protein expression of NR2B were obviously increased(P<0.05). Compared with SNI group, PMWT was significantly increased in SNI-CP group, the the protein and mRNA expression of SHH, GLI1 and BDNF were partly decreased, the protein expression of NR2B were partly decreased(P<0.05). Conclusions Inhibition of SHH signaling pathway can alleviate neuropathic pain in SNI rats and its mechanism may be related to the regulation of BDNF, NR2B in the spinal cord level.

Key words: 【Key words】SHH signaling pathway, cyclopamine, neuropathic pain, BDNF, NR2B

中图分类号: