中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (3): 673-681.doi: 10.4103/1673-5374.320997

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

微管动态变化在周围神经损伤后华勒变性和神经再生中的作用

  

  • 出版日期:2022-03-15 发布日期:2021-10-15

Role of microtubule dynamics in Wallerian degeneration and nerve regeneration after peripheral nerve injury

Jingmin Liu1, 2, Lixia Li1, 2, Ying Zou1, 2, Lanya Fu1, 2, Xinrui Ma1, 2, Haowen Zhang1, 2, Yizhou Xu1, 2, 3, Jiawei Xu1, 2, Jiaqi Zhang1, 2, Mi Li1, 2, Xiaofang Hu1, 2, Zhenlin Li1, 2, Xianghai Wang1, 2, 4, Hao Sun4, Hui Zheng4, Lixin Zhu3, Jiasong Guo1, 2, 3, 4, 5, *   

  1. 1Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China; 2Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong Province, China; 3Department of Spine Orthopedics, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China; 4Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 5Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, Guangdong Province, China
  • Online:2022-03-15 Published:2021-10-15
  • Contact: Jiasong Guo, PhD, jiasongguo@smu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82071386 (to JS), 81870982 (to JS) & 81571182 (to JS); the National Key Basic Research Program of China, No. 2014CB542202 (to JS); the Program for Changjiang Scholars and Innovative Research Team in University of China, No. IRT-16R37 (to JS); Key Research & Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR110104008 (to HZ); Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China, No. N201904 (to JS); and Natural Science Foundation of Guangdong Province of China, No. 2017A030312009 (to JS).

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摘要：

华勒变性是周围神经损伤后远端轴突和髓磷脂的渐进性崩解过程，其可为后续神经再生创造宽松的微环境，这一过程可能涉及细胞骨架的重建，但尚未见研究关注微管动力学在华勒变性中的作用。为解决这个问题，（1）实验利用微管稳定剂紫杉醇和微管解聚剂诺考达唑体外干预坐骨神经外植块。结果表明，紫杉醇诱导的微管稳定作用可促进轴突和髓鞘的变性以及许旺细胞的去分化；而诺考达唑诱导的微管解聚则抑制上述过程；（2）进一步对坐骨神经夹伤大鼠模型行紫杉醇和诺考达唑腹腔注射治疗，可见紫杉醇可加速轴突再生和神经传导，促进目标肌肉和运动行为的功能恢复，而诺考达唑则可产生相反的作用；（3）结果提示，微管动态变化可通过影响周围神经损伤后的华勒变性，进而参与周围神经的再生修复。实验于2015年10月15日经南方医科大学动物理论委员会批准（批准号SMU-L2015081）。

https://orcid.org/0000-0002-7885-2903 (Jiasong Guo) 

关键词: 华勒变性, 许旺细胞, 神经再生, 轴突脱髓鞘, 微管动力学, 紫杉醇, 诺考达唑, 周围神经损伤

Abstract: Wallerian degeneration, the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury, is essential for creating a permissive microenvironment for nerve regeneration, and involves cytoskeletal reconstruction. However, it is unclear whether microtubule dynamics play a role in this process. To address this, we treated cultured sciatic nerve explants, an in vitro model of Wallerian degeneration, with the microtubule-targeting agents paclitaxel and nocodazole. We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation, whereas nocodazole-induced microtubule destabilization inhibited these processes. Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration, as well as functional recovery of nerve conduction and target muscle and motor behavior, respectively. These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration. This study was approved by the Animal Care and Use Committee of Southern Medical University, China (approval No. SMU-L2015081) on October 15, 2015.

Key words: axon, demyelination, microtubule dynamics, nerve regeneration, nocodazole, paclitaxel, peripheral nerve injury, Schwann cell, Wallerian degeneration

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