中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1078-1085.doi: 10.4103/1673-5374.300459

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

抗坏血酸加速周围神经损伤后的Wallerian变性

  

  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:
    国家自然科学基金项目（81870982，81571182）；长江学者和高校创新团队计划（IRT-16R37）；国家重点基础研究计划（2014CB542202）；广东省科技计划项目（2015A020212024）；广州再生医学与健康广东实验室重点研发项目（2018GZR110104008）；广东省自然科学基金（2017A030312009）；广东省精神障碍重点实验室研究（N201904）

Ascorbic acid accelerates Wallerian degeneration after peripheral nerve injury

Lixia Li1, 2, 3, Yizhou Xu1, 2, Xianghai Wang1, 2, 5, Jingmin Liu1, 2, 5, Xiaofang Hu1, 2, 5, Dandan Tan1, 2, Zhenlin Li1, Jiasong Guo1, 2, 4, 5, 6, *   

  1. 1 Department of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong Province, China;  2 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong Province, China;  3 Department of Anatomy, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China;  4 Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;  5 Key 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, Southern Medical University, Guangzhou, Guangdong Province, China;  6 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Jiasong Guo, PhD, jiasongguo@smu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81870982 & 81571182; the Program for Changjiang Scholars and Innovative Research Team in Universities of China, No. IRT-16R37; the National Key Basic Research Program of China, No. 2014CB542202; the Science and Technology Project of Guangdong Province of China, No. 2015A020212024; Key Research & Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR110104008; the Natural Science Foundation of Guangdong Province of China, No. 2017A030312009, and Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China, No. N201904 (all to JG).

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摘要：

在周围神经损伤后发生的Wallerian变性有助于为神经再生提供有利微环境。作者既往研究发现抗坏血酸可能通过促进许旺细胞的增殖和吞噬，以及增强巨噬细胞的增殖、迁移和吞噬作用，促进周围神经再生。由于许旺细胞和巨噬细胞是参与Wallerian变性的主要细胞，因而测抗坏血酸可加速Wallerian变性。为检验该假设，实验在大鼠坐骨神经横断后即刻灌胃400 mg/kg抗坏血酸，随后每天灌胃200 mg/kg，同时使用200μM抗坏血酸干预大鼠坐骨神经外植块。结果发现抗坏血酸能显著促进横断神经和神经外植块中髓鞘碱性蛋白阳性髓鞘和神经丝200轴突的降解，同时还能抑制髓腔相关蛋白MAG表达，并促进c-Jun表达，增加巨噬细胞以及巨噬细胞中髓鞘碎片的数量。提示抗坏血酸加快损伤神经中的轴突和髓鞘退变，促进许旺细胞去分化，增强巨噬细胞募集及其吞噬能力，从而加快Wallerian变性。实验于2015年10月15日经南方医科大学动物伦理委员会批准，批准号：SMU-L2015081。

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

关键词: 抗坏血酸, Wallerian变性, 周围神经损伤, 轴突, 髓鞘, 许旺细胞, 巨噬细胞, 吞噬, 再生, 微环境

Abstract: Wallerian degeneration occurs after peripheral nerve injury and provides a beneficial microenvironment for nerve regeneration. Our previous study demonstrated that ascorbic acid promotes peripheral nerve regeneration, possibly through promoting Schwann cell proliferation and phagocytosis and enhancing macrophage proliferation, migration, and phagocytosis. Because Schwann cells and macrophages are the main cells involved in Wallerian degeneration, we speculated that ascorbic acid may accelerate this degenerative process. To test this hypothesis, 400 mg/kg ascorbic acid was administered intragastrically immediately after sciatic nerve transection, and 200 mg/kg ascorbic acid was then administered intragastrically every day. In addition, rat sciatic nerve explants were treated with 200 μM ascorbic acid. Ascorbic acid significantly accelerated the degradation of myelin basic protein-positive myelin and neurofilament 200-positive axons in both the transected nerves and nerve explants. Furthermore, ascorbic acid inhibited myelin-associated glycoprotein expression, increased c-Jun expression in Schwann cells, and increased both the number of macrophages and the amount of myelin fragments in the macrophages. These findings suggest that ascorbic acid accelerates Wallerian degeneration by accelerating the degeneration of axons and myelin in the injured nerve, promoting the dedifferentiation of Schwann cells, and enhancing macrophage recruitment and phagocytosis. The study was approved by the Southern Medical University Animal Care and Use Committee (approval No. SMU-L2015081) on October 15, 2015. 

Key words: ascorbic acid, axon, macrophage, myelin, peripheral nerve injury, phagocytosis, Schwann cell, Wallerian degeneration