周围神经损伤后经典的修复过程是远端需经历瓦勒氏变性, 重新由近端向远端生长，因再生缓慢而严重影响功能恢复。项目组前期研究证实采用轴突融合从细胞水平连接受损神经远近端，可避免瓦勒氏变性。但该法仅能使10%的轴突避免瓦勒氏变性，其原因是未及时修复细胞骨架。微管是细胞骨架的架构主干，所以重建微管通道是提高轴突融合效率的关键。众多研究表明微管切割蛋白spastin是引导微管形成的关键分子。因此本项目拟在轴突融合修复神经损伤的基础上，从spastin着手调控损伤处微管重塑，加强细胞骨架重建来提高疗效。采用免疫荧光染色等方法观察spastin在轴突损伤后微管重塑中的作用；通过电生理、组织学、神经示踪等方法评价外源性spastin蛋白联合轴突融合修复周围神经损伤的效果；最后观察spastin对AKT/GSK-3β/CRMP-2信号通路的影响，探索其调控微管重塑的机制，为治疗周围神经损伤提供一种新方法。

The classic regeneration process after peripheral nerve injury is that the distal end undergoes Wallerian degeneration and then it grows from the proximal end to distal end again. Because the regeneration speed is very slow, the functional recovery is seriously affected. Our previous studies have shown that the Wallerian degeneration can be avoided by axon fusion with connceting the proximal and distal ends of the damaged nerve. However, this method can only prevent 10% of axons from Wallerian degeneration.The reason is that the cytoskeleton is not repaired at the same time. Microtubule is the backbone of the cytoskeleton,and to reestablish the microtubule channel is the key step to improve the efficiency of axonal fusion. A lot of studies have showed that spastin, a kind of microtubule severing protein, plays an important role in the formation of microtubule, which may be a key molecule to reconstruct cytoskeleton in axon fusion. Therefore, this project aims to explore a new strategy for nerve repair, to avoid Wallerian degeneration of the distal ends of the injuried nerve by axon fusion; and to enhance cytoskeleton reconstruction by regulating the microtubule remodeling by spastin; At first, the effect of spastin on microtubule remodeling after axonal injury is observed by immunofluorescence staining; Secondly,the result of exogenous spastin protein combined with axonal fusion to repair peripheral nerve injury is evaluated by electrophysiology, histology, neural tracing and other methods; Finally, in order to explore the mechanism of microtubule remodeling regulated by spastin, the effect of spastin on AKT/GSK-3β/CRMP-2 signaling pathway was investigated. Through the above research, this project aimed to provide a new method for the treatment of peripheral nerve injury.