Nogo-c基因对周围神经损伤后远端靶器官萎缩与修复的影响及机制研究

After peripheral nerve injury ,distal targeted muscle atrophy is a urgent scientific problem to be solved in the field of peripheral nerve injury and repair. Nogo-C gene has abundant expression in skeletal muscle and the expression level changes after peripheral nerve injury.Preliminary experimental results show that:(1) The expression of Nogo-C gene showed a tendency of decrease first and then increase in the the early stage of nerve injury;(2) Nogo-C knockout can reduce muscle atrophy after nerve injury and promote its recovery. However, what is the cause of the down-regulated expression of Nogo-C gene in the early stage after nerve injury and convert to up-regulated gene expression rapidly? What is the rule of Nogo-C gene expression in muscle after nerve injury? What is the effect of different expression levels of Nogo-C gene on the targeted muscle atrophy and repair. These problems need to be further studied. The aim of this study is to study the effect of Nogo-C gene on the atrophy and repair of targeted muscle after peripheral nerve injury in a small gap repair model.We hope to reveal the mechanism of the gene in the repair of peripheral nerve injury and search for new entry points for the protection of distal target organs. The results will provide new ideas for the basic research on the protection of distal target organs after peripheral nerve injury and provide new direction for peripheral nerve repair.

神经损伤后远端靶器官的萎缩是周围神经损伤与修复领域迫切需要解决的科学问题。Nogo-C基因在骨骼肌内表达丰富,而且神经损伤之后其表达出现变化。前期实验结果显示：(1)神经损伤早期Nogo-C基因表达呈现出先降低后升高的趋势；(2)Nogo-C基因敲除可以减轻神经损伤后肌肉萎缩并促进其恢复。但是,周围神经损伤后Nogo-C基因表达降低，又迅速出现表达量上调的原因是什么？周围神经损伤后其支配肌肉中Nogo-C基因长期表达规律是什么？Nogo-C基因不同表达水平对靶肌肉萎缩的影响和机制是什么？这些问题都需要进一步研究。本课题拟在小间隙套接修复模型中，深入研究Nogo-C基因对周围神经损伤后靶肌肉萎缩与修复的影响。希望通过该研究进一步揭示该基因在周围神经损伤修复过程中的作用并寻求新的远端靶器官保护的切入点。其结果将为神经损伤后靶器官保护的基础研究提供新的思路，为神经修复提供新的干预方向。

神经损伤后远端靶器官的萎缩是周围神经损伤与修复领域迫切需要解决的科学问题。在周围神经损伤后患者常出现长期肢体功能障碍，严重影响生活质量。前期研究证实：Nogo-C基因在骨骼肌内表达丰富，且在失神经支配的骨骼肌中出现显著变化。但神经修复过程中Nogo-C对肌肉萎缩的作用及其机制尚不清楚。本研究深入研究了周围神经损伤后Nogo-C对失神经支配肌肉萎缩的影响及其作用机制；并分析了Nogo-C 基因对地塞米松诱导的成肌细胞萎缩的影响。研究结果显示：小鼠坐骨神经损伤后2周内，腓肠肌 Nogo-C 蛋白表达水平先升高后降低，在损伤后第7天达到最高，之后逐渐下降，第14天时，失神经腓肠肌内的Nogo-C含量远低于对照组。对于Nogo-C-/-小鼠，失神经支配肌肉萎缩速度变慢，肌纤维横截面积及肌肉湿重能更快恢复，运动终板保存更完整。在细胞水平上，过表达Nogo-C的成肌纤维细胞可见骨骼肌萎缩标记蛋白 Fbx32表达升高。.本课题研究了周围神经损伤后骨骼肌的Nogo-C表达变化以及其对肌肉萎缩的影响，并发现敲除Nogo-C基因可以抑制失神经支配肌肉的萎缩，促进其在重新获得神经支配后的功能恢复，可能为临床神经损伤后患者远端靶器官功能保护提供新的方向。