继发性脊髓损伤是脊髓损伤后重要的病理生理过程，具体发病机制不明。既往研究显示，巨噬/小胶质细胞极化参与继发性脊髓损伤的调控，影响了神经功能恢复（Chen J et al：2019 JN；2018 AM & FJ ）。研究表明，Notch信号通路激活依赖于Notch分子胞内亚基（NICD）的剪切及入核，在调控巨噬/小胶质细胞极化方面具有重要作用。本课题将在既往研究的基础上，通过建立脊髓损伤模型和巨噬/小胶质细胞极化模型，采用免疫杂交、免疫共沉淀、免疫荧光、基因敲除、过表达等技术，探讨继发性脊髓损伤时去乙酰化酶Sirt1调控NICD去乙酰化的特异性位点及对NICD与E3泛素化酶Fbxw7结合的影响，并进一步明确Fbxw7介导NICD泛素化的具体位点及调控NICD降解的泛素化类型。本研究将丰富巨噬/小胶质细胞极化的调控机制，为研究继发性脊髓损伤开辟新视角，也为临床预防和治疗脊髓损伤提供新思路。

Secondary spinal cord injury is an important pathophysiological process after spinal cord injury, and the specific pathogenesis is unknown. Our previous studies have shown that the polarization of macrophages/microglia participates in the regulation of secondary spinal cord injury and affects neurological recovery (Chen J et al：2019 J Neurotrauma；2018 Adv Mater & FASEB J). Recent studies have found that Notch signaling is involved in the regulation of macrophage/microglia polarization, which is dependent on the cleavage and nuclear translocation of the Notch molecular intracellular subunit (NICD). This project will explore the NICD-specific deacetylation sites regulated by acetylase Sirt1 and its effect on the binding NICD to Ubiquitin E3 ligase Fbxw7, and further clarify the specific sites of NICD ubiquitination and the ubiquitination type that regulates NICD degradation mediated by Fbxw7 by immunoblotting, immunoprecipitation, immunofluorescence, gene knock out and overexpression in the pinal cord injury model in vivo, and macrophage/microglia polarization model in vitro. This project will enrich the mechanism of macrophage/microglia polarization, open up new perspectives for the study of secondary spinal cord injury, and provide new ideas for clinical prevention and treatment of spinal cord injury.