中文摘要：

为了研究胶质细胞源性神经营养因子（GDNF）在中枢神经系统疾病中的治疗应用，运用基因突变、蛋白质融合表达和蛋白质纯化技术获得分子质量较小的GDNF（△N39）活性片段．将HIV-1 Tat蛋白转导区（protein transduction domain，PTD）的9个碱性氨基酸^49RKKRRQRRR^57模拟物9个精氨酸（R9）与GDNF（△N39）活性片段融合表达，获得纯度达95％以上的GDNF（△N39）-R9融合蛋白．将GDNF、GDNF（△N39）、GDNF（△N39）-R9分别加入原代培养的中脑多巴胺能神经元和转染GDNF受体GFRα1和Ret的PC12细胞中，观察它们的神经营养活性和毒性．运用脑微血管内皮细胞株B-Endo3，观察GDNF（△N39）-R9蛋白穿越血管内皮细胞膜的功能：运用脑血管内皮细胞和Matrigel铺板模拟血脑屏障，Transwell法检测Tat-GDNF（△N39）蛋白穿越脑血管内皮细胞和外周胶质膜的能力．结果显示：GDNF（△N39）-R9蛋白具有类似GDNF的神经营养活性，促进原代培养的中脑多巴胺能神经元和稳定表达GFRα1和Ret受体的PC12-GFRα1-Ret细胞株的存活，没有显示毒性，并且能很好地穿过脑微血管内皮细胞层和模拟的血脑屏障．

英文摘要：

In order to study the application of glial cell line-derived neurotrophic factor （GDNF） in clinic, gene mutation, fusion protein expression in E.coli and purification methods have been used to obtain the fragments of GDNF, GDNF（△N39）, GDNF（△N39）-Rg. Using primary cultured dopaminergic neurons and PC12 cells with transfected with GFRα1 and Ret to observe their biological function and cytotoxicity. Using B-Endo3 cells and Transwell method to analyze their delivery across the cellular membrane and blood brain barrier. The results show that GDNF （△N39）-R9 has the same neurotrophic function with wild GDNF and nearly no cytotoxicity to dopaminergic neurons and PC12-GFRα1-Ret cells and can get through effectually the cellular membrane and simulacrum of blood brain barrier with matrigel and B-Endo3.