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 (12): 2542-2548.doi: 10.4103/1673-5374.313054

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

DNA结合抑制剂2加速小鼠损伤坐骨神经的再生

  

  • 出版日期:2021-12-15 发布日期:2021-05-17
  • 基金资助:

    国家自然科学基金项目（82071369，81971198）；广东省国家“脑疾病治疗关键技术”基金项目（2018B00332001）；广州市脑科学与类脑智能技术重点项目（20200730090）；北京市自然科学基金（7192103）；广州再生医学与健康省级临床创新研究项目（2018GZR0201006）

Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

Zhong-Hai Huang1, Ai-Ying Feng1, Jing Liu1, Libing Zhou1, Bing Zhou2, *, Panpan Yu1, *   

  1. 1Guangdong-Hong Kong-Macau Institute of Central Nervous System Regeneration; Ministry of Education Joint International Research Laboratory of Central Nervous System Regeneration, Jinan University, Guangzhou, Guangdong Province, China; 2Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
  • Online:2021-12-15 Published:2021-05-17
  • Contact: Panpan Yu, PhD, yupanpan21@jnu.edu.cn; Bing Zhou, PhD, bingzh@buaa.edu.cn.
  • Supported by:
     This work was supported by the National Natural Science Foundation of China, Nos. 82071369 (to PY) and 81971198 (to BZ); Guangdong grant ‘Key Technologies for Treatment of Brain Disorders’ of China, No. 2018B030332001 (to LZ and PY); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology, China, No. 20200730090 (to LZ); the Natural Science Foundation of Beijing of China, No. 7192103 (to BZ); and the Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR0201006 (to PY).

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摘要：

DNA结合抑制剂2可在一定程度上促进中枢神经系统损伤后轴突的再生，但其是否也能促进周围神经损伤后轴突再生和功能恢复，目前尚不清楚。实验以挤压小鼠距三叉神经1 cm处坐骨神经30s建立双侧坐骨神经损伤模型，且于损伤前2周在T13双侧腹角注射6×1012病毒/mL的AAV9-Id2-3×Flag-GFP病毒以过表达DNA结合抑制剂2。结果显示，（1）DNA结合抑制剂2成功转染至投射到坐骨神经的脊髓运动神经元中，转染DNA结合抑制剂2的坐骨神经损伤后再生轴突数量更多，能再生至损伤部位远端超过3 mm处，且可延伸至腓肠肌；（2）损伤后2周时可见少量终板被运动轴突末端重新占据，1个月时发生广泛的神经肌肉神经支配；（3）腓肠肌复合肌肉动作电位波幅明显恢复，潜伏期显著缩短；（4）结果表明坐骨神经损伤后，DNA结合抑制剂2可加速轴突再生，促进神经肌肉的神经支配并增强神经功能，因而提升成年神经元中DNA结合抑制剂2水平可能是一种潜在的修复损伤周围神经的策略。实验于2016年3月2日经暨南大学实验动物伦理委员会批准，批准号20160302003。

https://orcid.org/0000-0002-4479-1479 (Panpan Yu)

https://orcid.org/0000-0002-7718-2311 (Bing Zhou)

关键词: DNA结合抑制剂2, 坐骨神经损伤, 轴突再生, 功能恢复, 运动神经元, 神经再支配, 周围神经, 神经肌肉接头

Abstract: Inhibitor of DNA binding 2 (Id2) can promote axonal regeneration after injury of the central nervous system. However, whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown. In this study, we established a mouse model of bilateral sciatic nerve crush injury. Two weeks before injury, AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord. Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve, and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury, arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle. By 1 month after injury, extensive neuromuscular reinnervation occurred. In addition, the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered, and their latency was shortened. These findings suggest that Id2 can accelerate axonal regeneration, promote neuromuscular reinnervation, and enhance functional improvement following sciatic nerve injury. Therefore, elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury. The study was approved by the Experimental Animal Ethics Committee of Jinan University (approval No. 20160302003) on March 2, 2016.

Key words: axonal regeneration, functional recovery, inhibitor of DNA binding 2, motor neuron, neuromuscular junctions, peripheral nerve, reinnervation, sciatic nerve injury

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