解剖学报

解剖学报 ›› 2019, Vol. 50 ›› Issue (1): 35-39.doi: 10.16098/j.issn.0529-1356.2019.01.007

• 神经生物学 • 上一篇    下一篇

抑制水通道蛋白4可降低脊髓后角胶质细胞细胞外调节蛋白激酶信号的活化改善坐骨神经损伤导致的神经病理性疼痛

赵亮1 李丹2 刘囡2 刘璐2 李洪鹏2*   

  1. 1.沈阳市第五人民医院骨外科， 沈阳 110023; 2.中国医科大学基础医学院解剖学教研室， 沈阳 110013
  • 收稿日期:2018-07-18 修回日期:2018-09-07 出版日期:2019-02-06 发布日期:2019-04-18
  • 通讯作者: 李洪鹏 E-mail:lihongpeng1966@hotmail.com
  • 基金资助:
    创伤性脑损伤后MAPK信号与Sirt1相互作用介导胶质细胞活化

 Inhibition of the aquaporin4 correlates with the analgesic effects via extracellular regulated protein kinase pathway activation of spinal dorsal horn after sciatic nerve injury

ZHAO Liang1 LI Dan2 LIU Nan2 LIU Lu2 LI Hong-peng2*   

  1. 1.Department of Bone Surgery, Shenyang Fifth People’s Hospital, Shenyang 110023, China; 2.Department of Anatomy, College of Basic Medical Science, China Medical University, Shenyang 110013, China
  • Received:2018-07-18 Revised:2018-09-07 Online:2019-02-06 Published:2019-04-18
  • Contact: LI Hong-peng E-mail:lihongpeng1966@hotmail.com

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摘要：

目的 探讨腰椎间盘突出引起的坐骨神经痛中，抑制水通道蛋白4（AQP4）对脊髓胶质细胞以及丝裂原活化蛋白激酶（MAPK）信号通路活化的影响。 方法 取8周龄雄性SD大鼠90只，分为假手术组18只，坐骨神经慢性压迫损伤(CCI)+DMSO组36只, CCI+TGN-020组（AQP4抑制剂）36只。CCI模型应用动物行为学，Western blotting方法，免疫荧光（双重染色）等方法检测。 结果 Western blotting显示，细胞外调节蛋白激酶（ERK）、c-Jun氨基末端激酶（JNK）、 p38MAPK信号通路及星形胶质细胞在神经损伤之后活化；免疫荧光在AQP4的表达被TGN-020抑制之后，胶质细胞及ERK、JNK、p38MAPK信号通路的活化被削弱，p-ERK和胶质纤维酸性蛋白（GFAP）共定位的细胞数量在损伤后明显增多，而TGN-020可减少之。 结论 抑制AQP4可抑制坐骨神经损伤引发的脊髓后角星形胶质细胞活化及MAPK信号通路活化，且可以通过抑制脊髓后角ERK通路的活化来抑制星形胶质细胞的活化，从而改善坐骨神经损伤所致神经病理性疼痛。

关键词: 坐骨神经损伤, 星形胶质细胞, 水通道蛋白4, 丝裂原活化蛋白激酶信号通路, 细胞外调节蛋白激酶信号通路, 免疫荧光, 大鼠

Abstract:

Objective To investigate the effect of inhibiting aquaporin 4(AQP4) on the activation of glial cells and mitogen-activated protein kinase(MAPK) signaling pathway in sciatica caused by lumbar disc herniation. Methods Male SD rats(n=90) were divided into sham group(n=18), chronic compressive injury(CCI)+DMSO group(n=36) and CCI+TGN-020 group(n=36). Make CCI model. Test sample of spinal by Western blotting method and immunology chemical fluorescence double staining method . Results Western blotting showed the astrocytes and extracellular regulated proptein kinase(ERK), c-Jun N-terminal kinase(JNK), p38MAPK pathway were activated. Immunofluorescence found TGN-020 could inhibit the expression of AQP4, weaken the activation of glial cells induced by nerve injury, and affected the activation of ERK,JNK and p38MAPK signaling pathways. We also found that the number of cells expressing p-ERK and glial fibrillary acidic protein(GFAP) at the same time increased obviously after injury, and could be significantly reduced by TGN-020. Conclusion Inhibition of AQP4 can inhibit the activation of astrocyte and activation of MAPK signaling pathway of spinal dorsal horn, which are caused by sciatic nerve injury. Inhibition of AQP4 can reduce the activation of astrocyte by inhibiting activation of the ERK pathway in the astrocytes in spinal dorsal horn, and improving the neuropathic pain caused by sciatic nerve injury.

Key words:  Sciatic nerve injury, Astrocytes, Aquaporin 4, Mitogen-activated protein kinase signal pathway, Extracellular regulated protein kinase signal pathway, Immunofluorescence, Rat