《中国康复理论与实践》

《中国康复理论与实践》

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脊髓损伤后神经再生相关信号通路研究进展①

吕威1a，姚海江2，莫雨平3，李冰1b，景泉凯1a，宋良玉1a，王鑫1a，李志刚1a，时素华4   

  1. 1.北京中医药大学，a.针灸推拿学院；b.基础医学院，北京市100029；2.中国康复研究中心北京博爱医院中医治疗中心，北京市100068； 3.深圳市第三人民医院康复科，广东深圳市518112；4.北京中医药大学第三附属医院康复科，北京市100029。
  • 出版日期:2016-03-25 发布日期:2016-06-01

Nerve Regeneration Related Signaling Pathway after Spinal Cord Injury (review)

LÜ Wei1a, YAO Hai-jiang2, MO Yu-ping3, LI Bing1b, JING Quan-kai1a, SONG Liang-yu1a, WANG Xin1a, LI Zhi-gang1a, SHI Su-hua4   

  1. 1. a. Department of Acupuncture and Massage; b. Department of Basic Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; 2. TCM Treatment Center, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China; 3. Department of Rehabilitation, the Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518112, China; 4. Department of Rehabilitation, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
  • Published:2016-03-25 Online:2016-06-01

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摘要： 随着神经再生相关机制研究不断深入，脊髓损伤后神经再生相关的信号通路也被广泛关注。有针对性地抑制细胞凋亡信号通路，可以降低脊髓损伤后细胞凋亡、炎症反应和神经变性。丝裂原活化蛋白激酶(MAPK)信号通路在调控基因表达、细胞增殖、细胞凋亡方面均发挥着重要作用，其下4 条通路之间尚存在着交互作用。Janus 激酶/信号转导子和转录激活子(JAK/STAT)信号通路除参与机体细胞的存活、增殖、分化、凋亡等过程外，还参与体内的炎性反应、氧化应激等过程。中枢神经系统损伤后，阻断Wnt信号通路可抑制神经轴突再生，而外源性Wnt3a 可以增加脊髓损伤后的神经元数量，促进轴突传导及神经功能的改善。脊髓损伤后抑制哺乳动物雷帕霉素靶蛋白(mTOR)信号通路，可以显著减少神经元丢失、细胞死亡等，而且可促进功能恢复。Notch信号通路激活时，神经干细胞增殖活跃，分化被抑制；信号通路被抑制时，干细胞进入分化阶段。Ras 同源基因/Rho 相关卷曲螺旋蛋白激酶(Rho/ROCK)信号通路激活导致生长锥塌陷、轴突再生受制，而选择性抑制Rho可促进脊髓损伤后轴突再生和运动功能恢复。

关键词: 脊髓损伤, 神经再生, 信号通路, 机制, 综述

Abstract: As the nerve regeneration has been researched more and more, nerve regeneration related signaling pathways after spinal cord injury (SCI) comes into the view. Inhibiting apoptosis signaling pathways may reduce the apoptosis, inflammation and nerve degeneration after SCI. Mitogen activated protein kinase (MAPK) signaling pathway plays an important role in regulation of gene expression, cell proliferation and apoptosis, and there was interaction among the four subordinate pathways. Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway does not only participate in the body cell survival, proliferation, differentiation and apoptosis, but also in the process of inflammatory and oxidative stress in the body. It has been found that blocking the Wnt signaling pathway after injury in the central nervous system would inhibit neural axon regeneration. Exogenous Wnt3a can increase the number of neurons after SCI and promote the axon conduction and nerve function. Inhibiting mammalian target of rapamycin (mTOR) signaling pathway after SCI can significantly reduce neuronal loss, cell death and well promote the functional recovery. When Notch signaling pathways are activated, neural stem cells proliferate actively and differentiation are inhibited, and stem cells enter the stage of differentiation as the pathway inhibited. Activation of Ras homolog gene/Rho associated coiled coil forming protein kinase (Rho/ROCK) signaling pathways leads to the collapse of the growth cone, inhibition of axon regeneration, whereas the selective inhibition of Rho can promote axon regeneration and recovery of motor function after SCI.

Key words: spinal cord injury, nerve regeneration, signaling pathways, mechanism, review