微管稳定性影响轴突修复的研究进展

摘要

中枢神经系统(central nervous system,CNS)损伤后常导致运动和感觉功能受损,给患者及其家庭带来沉重的经济和精神负担,损伤后神经功能恢复一直是医学界的难题.轴突作为神经元传导神经冲动的输出通道,将神经元细胞体发出的神经冲动传递给另一个或多个神经元或分布在肌肉、腺体的效应器,因此,轴突的再生修复是CNS功能恢复的重要途径之一.相关研究主要集中在细胞内各种信号途径对轴突再生的影响,而微管作为组成细胞骨架的主要结构,微管在生长锥内聚合组装是神经突延长、生长的基础.因此,无论哪种细胞内信号途径要实现对神经元轴突的有效再生,最终均要通过调控生长锥细胞骨架的微管来实现,只有微管稳定性较高而不影响微管聚合时才能促进轴突有效地再生修复.提高微管稳定性促进轴突修复的机制:通过增强钙离子激活的蛋白活性、增加受损部位的神经营养因子受体及上调一些蛋白如生长相关蛋白-43的表达而提升轴突再生反应;通过阻碍胶质瘢痕形成、抑制轴突变性、肿胀及回缩而减少轴突继发性损伤;削弱抑制因子的作用及提升轴突出芽生长能力等.因此,可从多种途径提高微管稳定性促进CNS轴突再生和神经功能恢复.未来的研究应在提高微管稳定性的基础上,综合采用多项措施促进CNS损伤后轴突的再生修复.%The injury of central nervous system (CNS) often results in irreversible sensory and motor impairments and the costs of money,energy are staggering for patients and their family.The successful functional recovery is a great challenge for surgeon.Axon is a long nerve fiber that conducts away from the cell body of the neuron to the effectors which distributed on muscles and glands,and the axonal regeneration is an ideal method for functional recovery.Many studies focus on various intracellular signaling pathways which are strongly related to the axonal regeneration.Microtubules are the main structures of the cytoskeleton,and the assembly of tubulin polymerization in the growth cone is the foundation of neurite elongation growth.Therefore,the pathways regulate the axonal regeneration by the microtubules and the strong microtubule dynamic stability which does not obstruct the assembly of tubulin polymerization could regenerate axon.The mechanisms of improving the microtubule dynamic stability to promote central nervous system axonal regeneration were as follows.It could enhance the activity of calcium-activated proteins,and increase the expression of neurotrophic factor receptor and growth-associated protein to promote the reaction of regenerative reaction.Improving microtubule dynamic stability could prevent the formation of glial scar,axonal degeneration,swelling and retraction,restrict the effect of neuronal inhibitory factors,and improve the ability of axonal sprouting.Therefore,increasing the dynamic stability of microtubule could promote the ability of axonal regeneration.A number of comprehensive measures should be investigated to promote axonal regeneration based on stable microtubule stability after CNS injury for future studies.