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 (3): 470-477.doi: 10.4103/1673-5374.202923

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

柚皮苷促进损伤脊髓再髓鞘化的作用途径

  

  • 收稿日期:2017-01-20 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    北京市自然科学基金（7164317）；北京清华长庚医院项目（12015c1028号）；国家自然科学基金项目（31400717）。

The mechanism of Naringin-enhanced remyelination after spinal cord injury

Wei Rong1, Yong-wei Pan1, Xu Cai1, Fei Song1, Zhe Zhao1, Song-hua Xiao1, Cheng Zhang2   

  1. 1 Department of Orthopedics, Beijing Tsinghua Changgung Hospital, Medical Center, Tsinghua University, Beijing Key Laboratory of Bioelectromagnetism, Beijing, China; 2 Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing, China
  • Received:2017-01-20 Online:2017-03-15 Published:2017-03-15
  • Contact: Song-hua Xiao, M.D. or Cheng Zhang, Ph.D., xiaosh301@aliyun.com or zhangchengcc@mail.iee.ac.cn.
  • Supported by:

    This study was supported by the Natural Science Foundation of Beijing of China, No. 7164317; the Beijing Tsinghua Changgung Hospital Fund, No. 12015C1028; the National Natural Science Foundation of China, No. 31400717.

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摘要：

课题组前期研究发现，柚皮苷灌胃治疗可提高损伤脊髓再髓鞘化水平，促进损伤脊髓神经功能的恢复。实验旨在进一步揭示柚皮苷促进少突胶质前体细胞分化成熟、促进髓鞘再生中的作用机制。实验设计采用重物击打法建立脊髓损伤大鼠模型，并柚皮苷灌羧甲基纤维素钠溶液灌胃(20，40 mg/kg)治疗4周后进行行为学评价、组织病理学染色、免疫荧光染色、电镜超微结构分析和生化分析。发现柚皮苷治疗可显著减轻脊髓损伤后脊髓白质脱髓鞘程度，增加皮质脊髓背侧束有髓神经纤维数量及髓鞘厚度，还可通过上调脊髓白质促细胞分化因子Nkx2.2和CNPase的表达，促进脊髓白质中少突胶质前体细胞分化，并抑制脊髓白质β-catenin/GSK-3β信号通路中β-catenin的表达及GSK-3β磷酸化。结果可证明，柚皮苷通过抑制β-catenin/GSK-3β信号通路调控少突胶质前体细胞分化，从而发挥促进脊髓损伤后髓鞘再生的作用。

ORCID:0000-0002-7975-5259(Song-hua Xiao); 0000-0002-9843-7977(Cheng Zhang)

关键词: 神经再生, 脊髓损伤, 柚皮苷, 再髓鞘化, 少突胶质前体细胞, 少突胶质细胞, &beta, -连环蛋白, 糖原合成酶激酶-3, 转录样蛋白2.2, 环核苷酸-3'磷酸水解酶, 行为学评价

Abstract:

Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg) for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β) phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.

Key words: nerve regeneration, spinal cord injury, naringin, remyelination, oligodendrocyte precursor cells, oligodendrocytes, β-catenin, glycogen synthase kinase-3β, NKx2.2, 2′,3′-cyclic nucleotide 3′-phosphodiesterase, behavioral assessment, neural regeneration