中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1847-1851.doi: 10.4103/1673-5374.363182

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

长链非编码RNA H19可抑制损伤周围神经的变性和再生

  

  • 出版日期:2023-08-15 发布日期:2023-02-24
  • 基金资助:
    国家自然科学基金项目（31971277，31950410551）；教育部归国学者科学研究基金项目；江苏省高等教育机构优先学术计划发展项目（PAPD）；江苏省研究生研究与实践创新计划项目（KYCX 19-2050）；江苏省大学生创新创业培训计划项目（202213993005Y）

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

Yu-Mei Feng1, #, Jian Shao1, #, Min Cai2, Yi-Yue Zhou1, Yi Yao3, Jia-Xi Qian1, Zi-Han Ding1, Mao-Rong Jiang1, Deng-Bing Yao1, *   

  1. 1School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Coinnovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 2Medical School of Nantong University, Nantong, Jiangsu Province, China; 3Nantong University Xinglin College, Nantong, Jiangsu Province, China
  • Online:2023-08-15 Published:2023-02-24
  • Contact: Deng-Bing Yao, MD, PhD, yaodb@ntu.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 31971277 (to DBY), 31950410551 (to DBY); Scientific Research Foundation for Returned Scholars, Ministry of Education of China (to DBY); a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (to DBY); the Postgraduate Research & Practice Innovation Program of Jiangsu Province of China, No. KYCX 19-2050 (to JS); and Jiangsu College Students’ Innovation and Entrepreneurship Training Program, No. 202213993005Y (to YY).

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摘要：

作者既往研究已发现长链非编码RNA H19可在大鼠坐骨神经损伤后华勒变性过程中的表达上调，且H19能促进许旺细胞的迁移，减缓背根神经节轴突的生长。但尚有研究确定H19在周围神经损伤后调控神经修复与再生的具体机制。为此，实验构建了坐骨神经横断大鼠模型，首先以原位杂交技术检测发现，在坐骨神经损伤后4-7d时，H19呈高表达。继而在损伤前14d时，于L4-L5鞘内注射腺相关病毒干扰和过表达H19，发现只有在过表达H19后，坐骨神经中新生轴突的生长受到抑制，而髓鞘形成则有所加强。继而以步态分析和热痛分析评估大鼠行为变化，可见过表达H19能延缓大鼠行为功能的恢复，而干扰H19表达后大鼠的行为则显著恢复。最后检验H19下游靶基因的表达变化，可见在H19过表达后，其下游因子SEMA 6D呈现高表达，进而引起轴突排斥反应，从而抑制轴突的生长。由此认为，H19可通过激活受伤神经中SEMA 6D，调节周围神经变性和再生，这为了解H19在周围神经变性和再生中的作用提供了新的线索。

https://orcid.org/0000-0002-5177-0318 (Deng-Bing Yao)

关键词: 长链非编码RNA H19, 背根神经节, 周围神经, 神经变性, 神经再生, 坐骨神经损伤, Wallerian变性, semaphorin 6D, 大鼠, 腺相关病毒

Abstract: Our previous studies have shown that long noncoding RNA (lncRNA) H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration, and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons. However, the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear. In this study, we established a Sprague-Dawley rat model of sciatic nerve transection injury. We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury, lncRNA H19 was highly expressed. At 14 days before injury, adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19. After overexpression of lncRNA H19, the growth of newly formed axons from the sciatic nerve was inhibited, whereas myelination was enhanced. Then, we performed gait analysis and thermal pain analysis to evaluate rat behavior. We found that lncRNA H19 overexpression delayed the recovery of rat behavior function, whereas interfering with lncRNA H19 expression improved functional recovery. Finally, we examined the expression of lncRNA H19 downstream target SEMA6D, and found that after lncRNA H19 overexpression, the SEMA6D protein level was increased. These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves. This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration. 

Key words: adeno-associated virus, dorsal root ganglion, lncRNA H19, nerve degeneration, nerve regeneration, peripheral nerve, rat, sciatic nerve injury, semaphorin 6D, Wallerian degeneration