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): 478-485.doi: 10.4103/1673-5374.202921

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

埃博霉素B抑制脊髓损伤后瘢痕形成的机制

  

  • 收稿日期:2017-02-06 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    山东省政府科技发展计划资助项目（2010gsf10254）；山东省医疗卫生科技计划项目（2015ws0504

Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injur

Wei Zhao1, Yong Chai2, Yun Hou3, Da-wei Wang1, Jian-qiang Xing1, Cheng Yang2, Qing-min Fang1   

  1. 1 Department of Spinal Surgery, Binzhou Medical University Hospital, Binzhou, Shandong Province, China; 2 Department of Anatomy, Binzhou Medical University, Yantai, Shandong Province, China; 3 Department of Histology and Embryology, Binzhou Medical University, Yantai, Shandong Province, China
  • Received:2017-02-06 Online:2017-03-15 Published:2017-03-15
  • Contact: Cheng Yang, M.D. or Qing-min Fang, yangchxn@163.com or byfqm2008@163.com.
  • Supported by:

    This work was supported by a grant from the Science and Technology Developing Program of Shandong Provincial Government of China, No. 2010GSF10254; a grant from the Medical and Health Science and Technology Plan Project of Shandong Province of China, No. 2015WS0504.

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摘要：

脊髓损伤后的纤维瘢痕形成一直被认为是阻碍神经轴突再生及功能恢复的主要障碍。已有研究证明抗肿瘤治疗药物埃博霉素B可抑制瘢痕形成，促进轴突生长，但具体机制尚不明确。为此，实验设计观察埃博霉素B对纤维瘢痕的主要成分-周细胞及细胞外基质的影响，探讨其对脊髓损伤后对纤维瘢痕形成的抑制效果。首先建立脊髓T10完全横断大鼠模型，随机分2组，于脊髓损伤后第1，15 d腹腔注射0.75 mg/kg 埃博霉素B干预为埃博霉素B组，设相同剂量生理盐水腹腔注射的Vehicle组作对比，作者发现相对于Vehicle组，埃博霉素B组损伤脊髓组织周细胞标记物神经元/胶质抗原2、血小板源生长因子受体β表达减少，纤维瘢痕基质中的纤维连接蛋白及胶原纤维蛋白表达明显减少，微管蛋白表达增多，而对胶质细胞纤维酸性蛋白几乎无影响，大鼠BBB评分增加。结果说明，埃博霉素B减少了损伤脊髓组织纤维瘢痕周细胞数量，抑制了细胞外基质生成，发挥了抑制脊髓损伤后纤维瘢痕形成的作用。

ORCID:0000-0002-7898-8376(Cheng Yang); 0000-0002-8388-8740(Qing-min Fang)

关键词: 神经再生, 脊髓损伤, 埃博霉素B, 周细胞, 基因表达, 纤维瘢痕, &beta, -微管蛋白, 血小板源生长因子受体&beta, 神经元/胶质抗原2, 纤维连接蛋白, 胶质细胞纤维酸性蛋白, 大鼠

Abstract:

Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury. A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra. The rats received an intraperitoneal injection of epothilone B (0.75 mg/kg) at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group. Neuron-glial antigen 2, platelet-derived growth factor receptor β, and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group, but β-tubulin protein expression was greater. Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment. The Basso, Beattie, and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group. The results of this study demonstrated that epothilone B reduced the number of pericytes, inhibited extracellular matrix formation, and suppressed scar formation after spinal cord injury.

Key words: nerve regeneration, spinal cord injury, epothilone B, pericytes, gene expression, fibrous scar, β-tubulin, platelet-derived growth factor receptor β, neuron-glial antigen 2, fibronectin, glial fibrillary acidic protein, rats, neural regeneration