肌萎缩侧索硬化小鼠内源性神经干细胞膜突触蛋白表达  

Synapsin expression of endogenous neural stem cell membrane in a mouse model of amyotrophic lateral sclerosis

作　　者：叶雪[1,2] 马春潮[2] 姚扬[2] 臧大维[2] 

机构地区：[1]天津医科大学,天津市300070 [2]天津市第一中心医院神经内科,天津市300192

出　　处：《中国组织工程研究》2013年第19期3527-3532,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家教育部回国人员科研启动基金资助(教外司留[2007]1108号);天津市卫生局攻关项目资助(11KG104)~~

摘　　要：背景:成纤维细胞生长因子2是神经系统主要的神经营养因子之一,目前已经被证明有促进内源性神经干细胞分化的作用。目的:观察成纤维细胞生长因子2干预下,肌萎缩侧索硬化SOD1G93AG1H转基因小鼠运动功能的改变,内源性神经干细胞的增殖情况,突触蛋白的水平改变及内源性神经干细胞增殖数目与突触蛋白水平改变的相关性。方法:取新出生SOD1G93AG1H转基因小鼠(肌萎缩侧索硬化模型小鼠)60只分为肌萎缩侧索硬化组及成纤维细胞生长因子2组各30只,取新出生野生B6SJL小鼠30只作为正常对照组,成纤维细胞生长因子2组腹腔注入成纤维细胞生长因子2;肌萎缩侧索硬化组和正常对照组腹腔注入安慰剂生理盐水。分别于出生后60,90,120d采用Rotarod方法评估小鼠运动功能的改变,采用免疫组织化学方法标记内源性神经干细胞和突触蛋白并计数,用spearman方法评估内源性神经干细胞增殖数目与突触蛋白水平的相关性。结果与结论:与肌萎缩侧索硬化组相比,成纤维细胞生长因子2组小鼠运动功能明显改善,内源性神经干细胞增殖和突触蛋白水平显著增高。小鼠内源性神经干细胞的增加与突触蛋白水平的增呈正相关。提示成纤维细胞生长因子2神经保护机制可能与其促进内源性神经干细胞增殖和提升突触蛋白水平相关。BACKGROUND：Fibroblast growth factor 2 is one of the main neurotrophic factors for nervous system, has been proved to have a role in promoting the differentiation of endogenous neural stem cel s. OBJECTIVE：To detect the improvement of motor behavior and the proliferation of endogenous neural stem cel s, the level of synapsin and the correlation between the differentiation number of endogenous neural stem cel s and the level of synapsin in the SOD1G93A G1H transgenic mouse model of amyotrophic lateral sclerosis after fibroblast growth factor 2 administration. METHODS：Sixty new born SOD1G93A G1H transgenic mice （mouse models of amyotrophic lateral sclerosis） were divided into amyotrophic lateral sclerosis group and fibroblast growth factor 2 group, 30 mice in each group. Thirty newborn wild B6SJL mice were col ected as normal control group. Mice in the fibroblast growth factor 2 group received intraperitoneal injection of fibroblast growth factor 2;the mice in the amyotrophic lateral sclerosis group and the normal control group received intraperitoneal injection of placebo normal saline. The improvement of motor behavior was evaluated with Rotarod test at postnatal 60, 90 and 120 days;immunohistochemistry was used to mark the endogenous neural stem cel s and count the synapsin;the correlation between the differentiation number of endogenous neural stem cel s and the level of synapsin was evaluated with Spearman statistical method. RESULTS AND CONCLUSION：Compared with the amyotrophic lateral sclerosis group, the fibroblast growth factor 2 group showed a statistical y significant improvement in the motor behavior, number of endogenous neural stem cel s and level of synapsin were significantly increased. There was a negative correlation between the differentiation number of endogenous neural stem cel s and level of synapsin. The neuro-protection mechanism of fibroblast growth factor 2 may be associated with the proliferation of endogenous neural stem cel s and level of synapsin.

关 键 词：干细胞 干细胞培养与分化 肌萎缩侧索硬化 成纤维细胞生长因子2 内源性神经干细胞 神经干细胞 突触蛋白 SOD1G93AG1H转基因小鼠 细胞因子 运动功能 转棒仪 部级基金 

分 类 号：R394.2[医药卫生—医学遗传学]