临床修复周围神经损伤多采用自体神经移植，但移植后神经向错误方向生长，无法顺利实现与下端所支配神经轴突的对接，成为周围神经再生与功能重建的瓶颈问题之一。有研究报道牵张力能牵引神经轴突的生长方向，但机制不明。申请人前期研究发现：一定的牵张力能激活Netrin-1（吸引信号），促进轴突延伸；同时激活Sema（排斥信号），引起轴突回缩，阻断轴突在错误方向上的生长，但是牵张力下Sema排斥机理尚未见报道。本项目拟从细胞和分子水平，研究牵张力作用下轴突的延伸生长与突触连接等，探究牵张力作用下Sema-Plexin通路的作用机制，及下游Rac1, CRMP2和Cofilin等的变化规律，通过SiRNA和过表达技术，找到阻断错误方向突触连接的关键调控子，探寻牵张力作用下阻断轴突回缩而延伸生长的具体作用及机理，以动物在体验证其在修复神经损伤中的作用，为周围神经再生提供重要的理论支持和临床实践新方法。

Nerve functional regeneration is very difficult during peripheral nerve repair, because regenerative neurons often grow in the wrong way, which result in the failure of functional synapse connection. Previous study indicated mechanical stretch can direct the axonal guidance and growth, but its molecular mechanism is not clear yet. During mechanical stretch loading, some attractive axonal guidance cue Netrin-1 was activated, but repulsion cue Sema was also activated, which can repel axon to leave wrong way. In this study, the molecular mechanism of Sema-Plexin signaling on axonal guidance growth after the mechanical stretch loading was investigated in the primary cultured DRG neurons. The axonal elongation and guidance were studied by IF and patch clamp assay etc. The role of RhoGTPase Rac, CRMP2 and Cofilin were investigated. In addition, it will find a key molecule to mediate the axonal guidance growth by SiRNA and overexpression assay, which can block the axonal connection in wrong way. The role of Sema-Plexin on axonal guidance growth will be investigated in vivo study . It will provide a new approach for nerve regeneration.