脊髓损伤后轴突生长抑制因子CSPGs及MAIFs与受体PTPσ及NgR相互作用，共同决定轴突的抑制作用。同时阻断CSPGs及MAIFs的抑制作用并阐明PTPσ及NgR介导的CSPGs及MAIFs的轴突抑制机制网络是脊髓损伤修复研究的关键步骤。课题组前期利用已获得的高抑制效率PTPσ-shRNA及NgR-shRNA，成功地构建了慢病毒介导lhRNA双基因干扰系统同时沉默PTPσ及NgR基因，本研究拟在此基础上：（1）探索同时阻断CSPGs及MAIFs对神经修复的影响；（2）应用神经元iTRAQ差异蛋白质组学及生物信息学技术，分析PTPσ及NgR双基因沉默后神经元蛋白质表达的改变，明确差异蛋白质，针对性地解析PTPσ及NgR介导的CSPGs及MAIFs的轴突抑制机制网络，初步阐明可能的主要轴突抑制及修复机制，为轴突生长抑制因子的阻断治疗及脊髓损伤的靶向治疗奠定理论基础。

CSPGs and MAIFs, two important axonal growth inhibitors after spinal cord injury, interact with their receptors (PTPσ and NgR) and result in the inhibition on axon growth in a combined action. It is a key step for studies on recovery of spinal cord injury to block inhibitory effects of CSPGs and MAIFs simultaneously, and to elucidate the inhibitory mechanisms network of CSPGs and MAIFs on axon growth mediated by PTPσ and NgR. Making use of the previously acquired PTPσ-shRNA and NgR-shRNA, we have successfully constructed the lentivirus-mediated lhRNA with high efficiency that silence PTPσ and NgR simultaneously. Based on these preliminary achievements, this study aims to investigate the effects of simultaneous blockage of CSPGs and MAIFs on the axon regeneration and elongation, as well as the neurological recovery, and analyze the proteomic changes of neurons after simultaneous blockage of PTPσ and NgR using iTRAQ differential proteomics and bioinformatics to reveal the differential proteins for the specific analysis of the PTPσ and NgR-mediated inhibitory mechanisms of CSPGs and MAIFs on axon growth，and preliminarily clarify the mainly potential mechanisms network of axonal inhibition and repair. This study would lay the foundation for blockage of axonal growth inhibitors and targeted therapy after spinal cord injury.