碱性成纤维细胞生长因子调节自噬及相关的泛素化蛋白降解系统在脊髓损伤恢复中的机制研究

项目名称： 碱性成纤维细胞生长因子调节自噬及相关的泛素化蛋白降解系统在脊髓损伤恢复中的机制研究

项目编号： No.81200958

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 张宏宇

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： 脊髓损伤（spinal cord injury, SCI）的治疗一直是神经医学研究领域的世界性难题。目前对于脊髓损伤的研究主要集中在继发性损伤恢复方面，有效抑制神经细胞死亡并提高其活力，是促进脊髓损伤修复和重建的首要目标。自噬是一种细胞通过溶酶体降解途径调控的细胞器和蛋白循环过程，同时与细胞泛素化蛋白代谢密切相关。本课题前期工作发现SCI过程中有明显的自噬激活，给予bFGF治疗能够促进SCI的恢复和重建；此外，应用bFGF处理能够显著抑制体外细胞模型中的自噬过程。因此，本项目拟在前期工作的基础上，采用大鼠脊髓损伤模型，首次探讨自噬在脊髓损伤中的具体作用及其对神经细胞的影响。应用生长因子药物bFGF治疗来促进脊髓损伤的恢复，观察自噬及相关泛素化蛋白降解在其中的作用。旨在为脊髓损伤的治疗和恢复研究提供全新的思路和药物靶点，也为bFGF等生长因子类药物的新药开发奠定更为全面和深入的理论基础。

中文关键词： 脊髓损伤；自噬；泛素化；碱性成纤维细胞生长因子；内质网应激

英文摘要： The therapy of spinal cord injury is a worldwide tough problem in the neural medical research. Currently, the studies on the spinal cord injury are mainly focus on the recovery of secondary lesion, to inhibit the cell death and improve the viability of neural cells, is the first target in the recovery of spinal cord injury. Autophagy is a process of organelles and proteins that cycled by lysosome, which also related to the metabolism of ubiquitinated protein. In our early research, we found that autophagy was activated significantly in the SCI process, treatment with bFGF improved the recovery of SCI;furthermore, the autophagy was inhibited by bFGF in vitro cell model. Thus, this project base on the early research fundament, use the mouse spinal cord injury model, investigate the role of autophagy in the spinal cord injury and the effect on neural cells firstly. Use the bFGF treatment to improve the recovery of spinal cord injury, demonstrate the role of autophagy and the relative degradation of ubiquitinated protein. Intend to supply new sight and pharmacal target for the therapy and recovery of spinal cord injury, also to establish the overall and deep theoretical foundation for the development of the new drugs of bFGF and the other growth factors.

英文关键词： spinal cord injury；autophagy；ubiquination；bFGF；ER stress