中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (11): 1816-1823.doi: 10.4103/1673-5374.194753

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

甲基强的松龙促进脊髓损伤后的神经功能恢复：与wnt/β-catenin信号通路激活有关？

  

  • 出版日期:2016-11-30 发布日期:2016-11-30
  • 基金资助:
    国家自然科学基金（81471854）

Methylprednisolone promotes recovery of neurological function afer spinal cord injury: association with Wnt/β-catenin signaling pathway activation

Gong-biao Lu1, Fu-wen Niu1, Ying-chun Zhang2, Lin Du3, Zhi-yuan Liang1, Yuan Gao1, Ting-zhen Yan1, Zhi-kui Nie1, *, Kai Gao1, *   

  1. 1 Department of Orthopedics, Jining No.1 People’s Hospital, Jining, Shandong Province, China 2 Department of Interventional Radiology, Jining No.1 People’s Hospital, Jining, Shandong Province, China 3 Jining Medical University, Jining, Shandong Province, China
  • Online:2016-11-30 Published:2016-11-30
  • Contact: Zhi-kui Nie or Kai Gao, 1756039110@qq.com or gaohaikai88@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81471854.

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摘要：

有研究表明，脊髓损伤后wnt/β-catenin信号通路被激活，其特异性蛋白LRP，β-catenin和GSK-3β等表达水平发生明显改变。我们以此假设脊髓损伤后甲基强的松龙可能通过激活wnt /β-catenin信号通路来促进神经功能的恢复。实验设计大鼠脊髓损伤后立即、术后第1，2天分别腹腔注射甲基强的松龙30 mg/kg。发现在脊髓损伤后2-6周，甲基强的松龙可明显地增加脊髓损伤大鼠BBB评分；脊髓损伤后第7天，甲基强的松龙减少了大鼠脊髓前角运动神经元的死亡，降低了脊髓后角损伤部位的面积；脊髓损伤后第3，7天，大鼠损伤脊髓组织神经细胞凋亡标志性蛋白caspase-3、caspase-9、Bax水平和凋亡细胞数量均可被甲基强的松龙抑制；脊髓损伤后第7天，抑凋亡因子Bcl-2水平则增强，同时甲基强的松龙还促进了大鼠损伤后第3，7天脊髓组织LRP-6和GSK-3β蛋白的磷酸化、上调了β-catenin的蛋白表达，以此激活了wnt/β-catenin信号通路。实验结果说明，甲基强的松龙促进脊髓损伤神经修复的保护作用可能与与wnt/β-catenin信号通路激活有关。 

orcid: 0000-0002-7158-1557 (Zhi-kui Nie),0000-0002-0771-7755 (Kai Gao)

关键词: 神经再生, 脊髓损伤, 神经保护, 甲基强的松龙, 凋亡, 运动功能, caspase-3, caspase-9, Bax, Bcl-2

Abstract: Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specifc proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are signifcantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery afer spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment signifcantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. Te number of surviving motor neurons increased, whereas the lesion size signifcantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. Tese results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway.

Key words: nerve regeneration, spinal cord injury, neuroprotection, methylprednisolone, apoptosis, locomotor function, caspase-3, caspase-9, Bax, Bcl-2, neural regeneration