摘要
目的 探讨TH基因修饰的神经干细胞脑内移植对帕金森病(PD)的治疗作用。方法构建pN2 ATH逆转录病毒载体质粒,用PA317细胞包装,G418筛选阳性克隆,病毒上清感染神经干细胞,将表达TH的神经干细胞植入PD大鼠纹状体内,测定PD大鼠旋转行为改善,DA和DOPAC含量变化,以及TH在纹状体的表达。结果 TH基因修饰的神经干细胞移植8周时能显著降低PD大鼠旋转行为,增加纹状体DA和DOPAC含量,TH在纹状体内的表达增加,疗效好于单纯神经干细胞移植组。结论TH基因修饰的神经干细胞移植对PD大鼠有明显的治疗作用,可望为PD治疗提供新的途径。
Objective To study therapeutic effect of intracerebral transplantation of TH -gene modified neural stem cells (NSCs) on PD rats. Methods The pN2ATH recombinant retroviral plasmids were transferred into PA317 cells with liposome. Resistant colonies were cloned and maintained under G418 selection, and the virus supernatants were harvested. The NSCs were incubated in N2ATH viral supernatant and selection under G418. NSCs and TH -gene modified NSCs were transplanted in the striatal areas of the PD model rats. At different time after transplantation the rats were tested for apomorphine-induced rotation. Their DA, DOPAC levels and TH expression in striatal areas were also analysed. Results The rotation of rats that had received grafts of TH-transduced NSCs revealed decreasing apparently 8 weeks after transplantation compared with that of the control graft group and NSCs group. The DA, DOPAC levels and TH expression in striatal areas of the PD rats receiving TH-transduced NSCs 8 weeks after transplantation were higher than that of receiving NSCs grafts and Saline grafts. Conclusion TH-gene modified NSCs have apparent effect on PD rats and might serve as an useful source of donor cells for the gene therapy of PD.
出处
《中华神经外科杂志》
CSCD
北大核心
2003年第5期375-379,共5页
Chinese Journal of Neurosurgery
基金
国家自然科学基金资助项目(39800046)
