中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (10): 1716-1723.doi: 10.4103/1673-5374.217352

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

睫状神经营养因子保护体外谷氨酸诱导背根神经节神经元损伤的作用

  

  • 收稿日期:2017-08-20 出版日期:2017-10-15 发布日期:2017-10-15
  • 基金资助:

    山东省自然科学基金（ZR2014HQ065）; 山东省医学技术发展项目（2015WS0445）

 In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

 Shu-yun Wen1, 2, Ai-min Li3, Kuan-qing Mi4, Rui-zheng Wang4, Hao Li5, Hua-xiang Liu2, Yi Xing1   

  1. 1 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
    2 Department of Rheumatology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
    3 Department of Rheumatology, Qingdao Fifth People’s Hospital, Qingdao, Shandong Province, China
    4 Department of Neurosurgery, Jinan Fifth People’s Hospital, Jinan, Shandong Province, China
    5 Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
  • Received:2017-08-20 Online:2017-10-15 Published:2017-10-15
  • Contact: Yi Xing, M.D., Ph.D.,xingyi2016@yahoo.com.
  • Supported by:

    This work was supported by the Natural Science Foundation of Shandong Province of China, No. ZR2014HQ065; a grant from the Medical Science and Technology Development Project of Shandong Province of China, No. 2015WS0445.

PDF

300

摘要：

睫状神经营养因子可通过磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase，PI3K)/Akt信号通路和Janus激酶2(Janus kinase 2，JAK2)/信号转导子和转录激活子3(signal transducer and activator of transcription 3，STAT3）通路激活，发挥其神经保护作用。然而，睫状神经营养因子对谷氨酸导致的背根神经节兴奋性毒性是否具有保护作用尚有待研究。实验以原代培养的Wistar大鼠胚胎15 d背根神经节神经元谷氨酸兴奋性毒性，来验证睫状神经营养因子的神经保护作用，同时检测与睫状神经营养因子保护作用相关的JAK2/STAT3与PI3K/Akt信号通路的变化。结果显示，谷氨酸所诱导的背根神经节神经元突起生长受到抑制，细胞活力下降，生长相关蛋白43表达减少，凋亡神经元比例增加，caspase-3表达水平上调，外源性睫状神经生长因子干预可缓解背根神经节神经元的兴奋性毒性。利用JAK2抑制剂AG490或PI3K抑制剂LY294002预孵育可阻断睫状神经生长因子的神经保护作用。事实更说明，睫状神经营养因子对谷氨酸诱导背根神经节神经元损伤有神经保护作用，其机制与JAK2/STAT3和PI3K/Akt通路的调节有关。

orcid:0000-0001-7594-8398(Yi Xing)

关键词: 神经再生, 睫状节神经生长因子, JAK2/STAT3 , PI3K/Akt , 谷氨酸, 神经元, 兴奋性毒性, 神经保护作用, 生长相关蛋白43 , 神经突起生长, 背根神经节

Abstract:

Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase (JAK) 2/activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood. In the present study, the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15. Whether the JAK2/STAT3 and PI3K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined. Glutamate exposure inhibited neurite outgrowth, cell viability, and
growth-associated protein 43 expression and promoted apoptotic neuronal cell death, all of which were reversed by the administration of exogenous ciliary neurotrophic factor. Additionally, preincubation with either JAK2 inhibitor AG490 or PI3K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor. These data indicate that the two pathways JAK2/STAT3 and PI3K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.

Key words: nerve regeneration, ciliary neurotrophic factor, JAK2/STAT3, PI3K/Akt, glutamate, neuron, excitotoxicity, neuroprotection, growth-associated protein 43, neurite outgrowth, dorsal root ganglion, neural regeneration