SUMO促进创伤性颅脑损伤神经修复的研究

项目名称： SUMO促进创伤性颅脑损伤神经修复的研究

项目编号： No.81501073

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张琳

作者单位： 天津市第五中心医院

项目金额： 17.5万元

中文摘要： 脑外伤后有较高的致死及致残率,我们致力于提高损伤细胞的自我保护机制以及内源性神经再生的能力来促进神经修复。SUMO(Small ubiquitin-like modifier)是一种类似于泛素的蛋白质,发挥蛋白质翻译后修饰的作用, 能够调节多种信号通路，在缺血性脑损伤中有明确的细胞保护作用，我们首次提出SUMO在脑创伤后也必定发挥多通道的神经保护作用。本课题组前期研究发现,在创伤灶周围和创伤侧海马及脑室呈现出明显的SUMO化现象；创伤灶周围的神经元和星形胶质细胞中都存在SUMO化现象。接下来,我们将全面检测脑外伤后SUMO的表达,并运用SUMO敲低的转基因小鼠来研究SUMO在脑外伤后神经修复的作用,最后运用Microarray分析的方法发现脑创伤后SUMO调节的主要基因及信号转导通路。为后续研究SUMO在脑创伤中发挥神经修复作用的分子机制及药物开发奠定基础,为临床治疗脑创伤提供新思路。

中文关键词： 创伤性颅脑损伤；SUMO；神经保护；神经再生

英文摘要： The high mortality and morbidity after traumatic brain injury (TBI) threaten the public health. We devote to promoting restoration of nervous system by improving the self-protection of injured cells and endogenous neurogenesis of stem cells. SUMO (Small ubiquitin-like modifier) is a group of proteins, which could conjugate to the target protein to regulate the post-translational process and regulate plenty of signaling pathway. The ischemia-induced activation of SUMO conjugation is shown to be a protective response of post-ischemic neurons. We hypothesize that SUMO has a neuroprotective effect after TBI. Our group observed the sumoylation in the territory border, hippocampus and ventricular zone from the ipsilateral hemispheres after TBI. We also found the sumoylation both in neuron and astrocyte. We will detect the SUMO expression following injury and use SUMO knockdown transgenic mice to observe SUMO function for nervous repair after TBI. Finally, we will detect the main gene and signaling pathway related to sumoylation after TBI. These researches will provide some basic theory toward further study for molecular mechanism and drug therapy, which will be as a candidate for future neurotherapeutic intervention following TBI.

英文关键词： Traumatic brain injury;SUMO;Neuroprotective;Neurogenesis