中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (8): 1477-1485.doi: 10.4103/1673-5374.235306

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

新方法构建慢性神经卡压大鼠模型

  

  • 收稿日期:2018-06-15 出版日期:2018-08-15 发布日期:2018-08-15
  • 基金资助:

    中国国家自然科学基金项目(81471270

A novel chronic nerve compression model in the rat

Zhen-Yu Liu, Zhen-Bing Chen, Jiang-Hai Chen   

  1. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Received:2018-06-15 Online:2018-08-15 Published:2018-08-15
  • Contact: Zhen-Bing Chen or Jiang-Hai Chen,739250311@qq.com or chenjianghai@hust.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81471270

摘要:

现有的动物慢性周围神经卡压模型主要是硅胶管模型,然而大鼠的坐骨神经的横截面并非正圆形,并且因个体差异的原因,其坐骨神经直径存在差别。使用统一内径的硅胶管,可能会使实验结果出现误差。我们希望能建立一种既能引起坐骨神经脱髓鞘变化,又能导致骨骼肌萎缩的大鼠坐骨神经慢性卡压模型。为此,实验设计暴露SD乳鼠或成年大鼠右后肢坐骨神经,将一片乳胶放置在神经下,滴加约5μL N-丁基-氰基丙烯酸酯,其上覆盖另一片乳胶,形成夹心状复合体,建立慢性神经卡压模型。并以单独乳胶或和N-丁基-氰基丙烯酸酯包裹造模的乳鼠作为对照。以热板实验和电生理分析评估坐骨神经功能的变化,以免疫荧光染色和电镜量化神经病理学变化程度,以Masson染色评估腓肠肌和后爪内侧肌肉纤维化的程度。发现相比于成年大鼠和单独乳胶或和N-丁基-氰基丙烯酸酯包裹造模的乳鼠,新方法制作的慢性神经卡压乳鼠损伤后2周出现热感觉衰退,神经传导速度明显下降,8周坐骨神经显示脱髓鞘和轴突不规则表现,并引发受累神经的神经外膜和神经束膜中胶原沉积,20周时腓肠肌和后爪内侧肌肉纤维化程度明显增加。说明这种新方法制作的慢性神经卡压大鼠模型能够重现人慢性神经卡压损伤的功能和组织学变化特征,适合作为研究慢性神经卡压病理机制的新工具。

 

orcid:0000-0001-9712-6854(Jiang-Hai Chen)

关键词: 慢性神经卡压, 腕管综合症, 神经传导速度, N-丁基-氰基丙烯酸酯, 感觉衰退, 脱髓鞘, 髓鞘再生, 肌肉, 胶原沉积, 轴突不规则, 神经再生

Abstract:

Current animal models of chronic peripheral nerve compression are mainly silicone tube models. However, the cross section of the rat sciatic nerve is not a perfect circle, and there are differences in the diameter of the sciatic nerve due to individual differences. The use of a silicone tube with a uniform internal diameter may not provide a reliable and consistent model. We have established a chronic sciatic nerve compression model that can induce demyelination of the sciatic nerve and lead to atrophy of skeletal muscle. In 3-week-old pups and adult rats, the sciatic nerve of the right hind limb was exposed, and a piece of surgical latex glove was gently placed under the nerve.N-butyl-cyanoacrylate was then placed over the nerve, and after it had set, another piece of glove latex was placed on top of the target area and allowed to adhere to the first piece to form a sandwich-like complex. Thus, a chronic sciatic nerve compression model was produced. Control pups with latex or N-butyl-cyanoacrylate were also prepared. Functional changes to nerves were assessed using the hot plate test and electromyography. Immunofluorescence and electron microscopy analyses of the nerves were performed to quantify the degree of neuropathological change. Masson staining was conducted to assess the degree of fibrosis in the gastrocnemius and intrinsic paw muscles. The pup group rats subjected to nerve compression displayed thermal hypoesthesia and a gradual decrease in nerve conduction velocity at 2 weeks after surgery. Neuropathological studies demonstrated that the model caused nerve demyelination and axonal irregularities and triggered collagen deposition in the epineurium and perineurium of the affected nerve at 8 weeks after surgery. The degree of fibrosis in the gastrocnemius and intrinsic paw muscles was significantly increased at 20 weeks after surgery. In conclusion, our novel model can reproduce the functional and histological changes of chronic nerve compression injury that occurs in humans and it will be a useful new tool for investigating the mechanisms underlying chronic nerve compression.

Key words: nerve regeneration, chronic nerve compression, carpal tunnel syndrome, nerve conduction velocity, N-butyl-cyanoacrylate, hypoesthesia, demyelination, remyelination, intrinsic muscles, collagen deposition, axonal irregularity, neural regeneration