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 (9): 1538-1543.doi: 10.4103/1673-5374.215266

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

小间隙套接修复损伤坐骨神经近端组织许旺细胞的表型变化

  

  • 收稿日期:2017-06-22 出版日期:2017-09-15 发布日期:2017-09-15
  • 基金资助:

    山东科学研究中国青年科学家基金（bs2012yy019）

Phenotypic changes of Schwann cells on the proximal stump of injured peripheral nerve during repair using small gap conduit tube

Shi-jun Zhang1, Wen-liang Wu1, Kai-yun Yang2, Yun-zhen Chen1, Hai-chun Liu1   

  1. 1 Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
    2 Laboratory of Ears, Nose, and Throat, Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
  • Received:2017-06-22 Online:2017-09-15 Published:2017-09-15
  • Contact: Hai-chun Liu, M.D.,qiluorthowu@126.com or qiluorthozhsj@126.com.
  • Supported by:

    This study was supported by the Shandong Science and Research Foundation for Youth Scientists in China, No. BS2012YY019.

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摘要：

 

许旺细胞去分化是周围神经损伤和髓鞘形成的一个重要特征，许多特定的负性髓鞘化调节因子在此进程中起到了调节作用。以往类似研究多关注远端神经残端，其中Notch信号通路激活促进细胞分化和损伤神经修复，但对于周围神经损伤近端许旺细胞表型变化及Notch信号通路之间的关系探讨尚不明确。为此，实验构建坐骨神经横断伤模型大鼠，分为小间隙套接组和对照组，分别对其损伤神经断端进行壳聚糖套管小间隙套接修复和神经外膜缝合。免疫荧光染色发现，在伤后第1天，两组损伤近端髓鞘化许旺细胞中胶质纤维酸性蛋白表达上调，小间隙套接组在伤后第5天胶质纤维酸性蛋白表达最高，尽管它们此时仍与轴突紧密接触。与神经外膜缝合组相比，小间隙套接组伤近端损伤后前2周Notch1 mRNA表达明显升高。实时PCR检测结果发现，在伤后第3-14天，小间隙套接组损伤近端Hes1 mRNA表达较神经外膜缝合组显著升高。两组NICD mRNA表达变化趋势与Hes1 mRNA基本一致。结果证实，小间隙套接修复损伤坐骨神经近端组织许旺细胞表型发生了改变，活化的Notch信号通路在坐骨神经损伤早期起到了重要作用。

orcid:0000-0003-2566-4500(Hai-chun Liu)

关键词: 神经再生, 周围神经损伤, 坐骨神经, 许旺细胞, 神经横断伤, 小间隙套接法, 壳聚糖, Notch信号通路, Notch1, Hes1, 胶质纤维酸性蛋白, S100

Abstract:

Dedifferentiation of Schwann cells is an important feature of the response to peripheral nerve injury and specific negative myelination regulators are considered to have a major role in this process. However, most experiments have focused on the distal nerve stump, where the Notch signaling pathway is strongly associated with Schwann cell dedifferentiation and repair of the nerve. We observed the phenotypic changes of Schwann cells and changes of active Notch signaling on the proximal stump during peripheral nerve repair using small gap conduit tubulization. Eighty rats, with right sciatic nerve section of 4 mm, were randomly assigned to conduit bridging group and control group (epineurium suture). Glial fibrillary acidic protein expression, in myelinating Schwann cells on the proximal stump, began to up-regulate at 1 day after injury and was still evident at 5 days. Compared with the control group, Notch1 mRNA was expressed at a higher level in the conduit bridging group during the first week on the proximal stump. Hes1 mRNA levels in the conduit bridging group significantly increased compared with the control group at 3, 5, 7 and 14 days post-surgery. The change of the Notch intracellular domain shared a similar trend as Hes1 mRNA expression. Our results confirmed that phenotypic changes of Schwann cells occurred in the proximal stump. The differences in these changes between the conduit tubulization and epineurium suture groups correlate with changes in Notch signaling.This suggests that active Notch signaling might be a key mechanism during the early stage of neural regeneration in the proximal nerve stump.
 

Key words: nerve regeneration, Schwann cells, nerve injury, small gap conduit therapy, chitin, peripheral nerve injury, Notch signaling, Notch1, Hes1, glial fibrillary acidic protein, S100, neural regeneration