中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (5): 876-885.doi: 10.4103/1673-5374.249236

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

神经干细胞移植抑制脊髓损伤大鼠胶质细胞增殖和P2XR受体介导的神经病理性疼痛

  

  • 出版日期:2019-05-15 发布日期:2019-05-15
  • 基金资助:

    山东省自然科学基金(ZR2014HM046，ZR2015HL，ZR2014HL101)；中国泰安市科技发展项目(2015NS2183)

Neural stem cell transplantation inhibits glial cell proliferation and P2X receptor-mediated neuropathic pain in spinal cord injury rats

Xiao-Jing Du 1 , Yue-Xia Chen 1 , Zun-Cheng Zheng 1 , Nan Wang 2 , Xiao-Yu Wang 1 , Fan-E Kong 2   

  1. 1 Department of Rehabilitation Medicine, the Central Hospital of Taian, Taian, Shandong Province, China
    2 Graduate School, Taishan Medical University, Taian, Shandong Province, China
  • Online:2019-05-15 Published:2019-05-15
  • Contact: Zun-Cheng Zheng, MS, zxyyzhengzuncheng@126.com.
  • Supported by:

    This research was financially supported by the Natural Science Foundation of Shandong Province of China, No. ZR2014HM046 (to ZCZ), ZR2015HL113 (to XJD), and ZR2014HL101 (to XYW); the Science and Technology Development Project of Taian City of China, No.2015NS2183 (to XJD).

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摘要：

P2X4和P2X7受体在脊髓损伤后的神经性疼痛中发挥了重要作用，调控P2X4和P2X7受体可以显著降低损伤后的疼痛超敏反应。为了解神经干细胞移植对P2X受体介导的神经病理性疼痛的调节作用，并探讨其机制，实验设计用重物自由落体打击法，以胸10节段脊髓为中心，制作脊髓损伤模型大鼠。将神经干细胞局部注射到受损的脊髓节段，通过免疫组织化学和Western blot分析，测定P2X4、P2X7受体，神经丝蛋白，胶质纤维酸性蛋白表达水平；使用感觉阈值测定的方法定量评估大鼠感觉功能；BBB评分评估大鼠运动能力；热缩足时间评定大鼠神经病理性疼痛。结果显示：(1)神经干细胞移植4周后，损伤节段脊髓神经丝蛋白表达显著增加，胶质纤维酸性蛋白表达下降，P2X4和P2X7受体表达降低，大鼠的运动及感觉功能明显改善，神经病理性疼痛明显减轻；(2)结果验证了，神经干细胞移植可降低P2X4R和P2X7R的过度表达，促进感觉和运动功能重建，并在脊髓损伤后神经病理性疼痛的调节中起重要作用。故作者认为，神经干细胞移植可能是减轻P2X受体介导的神经病理性疼痛的有转化意义的方法之一。

orcid: 0000-0002-2998-1266 (Zun-Cheng Zheng)

关键词: 细胞移植, 感觉神经功能, 胶质纤维酸性蛋白, 神经丝蛋白, P2X4受体, P2X7受体, 小胶质细胞, 感觉阈值, 后肢运动功能, 胶质增生, 神经再生

Abstract:

P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-me¬diated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a mi¬cro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuro¬pathic pain mediated by P2X receptors.

Key words: nerve regeneration, cell transplantation, sensory nerve function, glial fibrillary acidic protein, neurofilament, P2X4 receptor, P2X7 receptor, microglial cells, perception threshold, hind limb function, glial hyperplasia, neural regeneration