中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 331-339.doi: 10.4103/1673-5374.226429

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

健侧C7神经移植跨半球功能重组的蛋白质组学分析

  

  • 收稿日期:2017-10-21 出版日期:2018-02-15 发布日期:2018-02-15

 Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer

Yin Yuan1, 2, 3, Xiu-yue Xu1, 2, 3, Jie Lao1, 2, 3, Xin Zhao1, 2, 3   

  1. 1 Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China
    2 Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai, China
    3 Shanghai Key Laboratory of Peripheral Nerve & Microsurgery, Shanghai, China
  • Received:2017-10-21 Online:2018-02-15 Published:2018-02-15
  • Contact: Xin Zhao, Ph.D.,drzhaox@sina.com.

摘要:

神经移植是全臂丛神经撕脱伤最常规的治疗方法,而在移植后损伤侧肢体的运动功能可在早期恢复阶段被健侧肢体的某些运动行为激活,即存在跨半球功能重组的现象。既往研究关注了fMRI影像以及脑源性神经营养因子和生长相关蛋白43等蛋白的变化,但尚无蛋白组学方面的研究。因此,实验设计对健侧C7神经移位治疗全臂丛神经撕脱伤模型大鼠,以基于稳定同位素标记的定量蛋白质组学技术筛选大鼠双侧大脑运动皮质中差异表达蛋白,已揭示其机制。发现上肢对应的大脑运动皮质部位中的差异表达蛋白大多数与神经系统的发育和功能,包括神经元的分化和发育,轴突生长和导向,微管和细胞骨架的重建,突触可塑性以及神经冲动传导相关,其中NFL和Thy-1是2种重要的分化相关蛋白。健侧大脑运动皮质中,移植后2周时NFL表达上调,而1-5个月时NFL表达下调;而Thy-1在移植后1-5个月时表达上调。损伤侧大脑运动皮质中NFL在移植后1-5个月时表达上调。Western blot结果与蛋白质组学结果一致。这些数据说明NFL和Thy-1可能在健侧C7神经移植跨半球功能重组中发挥重要作用。

orcid:0000-0003-0651-2608(Xin Zhao)

 

关键词: 神经再生, 臂丛神经, 健侧C7, 基于稳定同位素标记的定量分析, 蛋白质组学, 皮质重组, 大脑可塑性, 神经传导, NFL, Thy-1

Abstract:

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function (including neuron differentiation and development, axonogenesis,and guidance), microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light (NFL) and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteomic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer.

Key words: nerve regeneration, brachial plexus, brain plasticity, contralateral C7, cortex reorganization, isobaric tags for relative and absolute quantitation, proteomics, nerve transfer, neurofilament light, Thy-1, neural regeneration