中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 951-957.doi: 10.4103/1673-5374.158360

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

雷帕霉素保护损伤脊髓的wnt/β-catenin信号通路

  

  • 收稿日期:2015-03-13 出版日期:2015-06-18 发布日期:2015-06-18
  • 基金资助:

    中国国家自然科学基金项目(81171799, 81471854),博士后启动基金(2013T60948)

Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

Kai Gao 1, Yan-song Wang 1, Ya-jiang Yuan 1, Zhang-hui Wan 1, Tian-chen Yao 1, Hai-hong Li 1, Pei-fu Tang 2, Xi-fan Mei 1   

  1. 1 Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning Province, China
    2 Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
  • Received:2015-03-13 Online:2015-06-18 Published:2015-06-18
  • Contact: Xi-fan Mei, Ph.D. or Pei-fu Tang, Ph.D., meixifan1971@163.com or pftang301@163.com.
  • Supported by:

    This work was supported by grants from the National Natural Science Foundation of China, No. 81171799, 81471854 and a Special Financial Grant from the China Postdoctoral Science Foundation, No. 2013T60948.

摘要:

wnt/β-catenin信号通路在神经发育、轴突导向、神经病理性疼痛缓解和神经元存活中起着重要的作用。我们假设脊髓挫伤后雷帕霉素能对wnt/β-catenin信号通路产生影响,因此对脊髓挫伤模型大鼠连续2d腹腔注射雷帕霉素进行干预。应用Western blot及免疫荧光染色检测wnt/β-catenin信号通路,发现注射雷帕霉素的大鼠损伤脊髓组织中β-catenin和脑源性神经营养因子及抑制凋亡蛋白caspase-3 呈高表达,促进脊髓损伤区病理形态的改善,减少运动神经元的丢失,促进了脊髓损伤大鼠运动功能的恢复,说明雷帕霉素干预后脊髓损伤大鼠神经保护作用的途径在于激活了wnt/β-catenin信号通路。

关键词: 神经再生, 脊髓损伤, 雷帕霉素, Wnt/β-catenin信号通路, 细胞凋亡, caspase-3, 脑源性神经营养因子, 神经保护, 神经元丢失

Abstract:

The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

Key words: nerve regeneration, spinal cord injury, rapamycin, Wnt/β-catenin signaling pathway, apoptosis, caspase-3, brain-derived neurotrophic factor, neuroprotection, loss of neurons, NSFC grants, neural regeneration