Nurr1基因修饰胚胎中脑神经干细胞移植治疗帕金森病

Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’s Disease

目的探讨移植Nurr1基因修饰胚胎中脑神经干细胞对帕金森大鼠的治疗效果。方法(1)建立SD大鼠帕金森病模型;(2)原代培养SD大鼠胚胎中脑神经干细胞,并于神经干细胞过表达Nurr1;(3)移植治疗分组:假手术组(A组),移植神经干细胞组(B组),移植Nurr1修饰神经干细胞组(C组);(4)在移植后3周、6周、9周和12周分别对各组大鼠进行行为学测试,观察各组症状改善情况;(5)移植12周后,分别检测各组中Nurr1、TH蛋白表达情况和Nurr1荧光情况。结果(1)原代培养大鼠胚胎中脑神经干细胞,并于神经干细胞成功过表达Nurr1基因。(2)免疫荧光、Western Blot证实过表达Nurr1可以促进神经干细胞向多巴胺能神经元转化(P<0.05)。(3)移植Nurr1修饰神经干细胞可以有效的改善帕金森大鼠的症状(P<0.05),Western Blot证实小胶质细胞可显著促进移植后的神经干细胞在分化为多巴胺能神经元(P<0.05)。(4)移植后Nurr1能促进神经干细胞向多巴胺能神经元转化,提高移植神经干细胞的存活,达到更好治疗效果。结论Nurr1基因可以促进神经干细胞向多巴胺能神经元转化;移植修饰Nurr1神经干细胞可以有效治疗帕金森大鼠。

Objective To investigate the therapeutic effect of transplanted Nurr1 gene-modified embryo midbrain neural stem cells in Parkinson’s rats. Methods 1. Establishment of Parkinson’s disease animal model in SD rats. 2. Primary culture of embryo midbrain neural stem cells(NCSs) and Nurr1 gene-modified neural stem cells.3. Grouping: sham operation group( sham group), Transplanted neural stem cell group( NCS group),transplanted Nurr1 gene-modified neural stem cells group(NNCS group). 4. At 3 weeks,6 weeks,9 weeks,and 12 weeks after the transplantation, the behavioral tests of rats in each group were performed to observe the improvement of symptoms in each group. 5. After 12 weeks of transplantation,the expression of Nurr1,TH protein and Nurr1 fluorescence were detected in each group. Results 1. Primary cultured neural stem cells, and successfully overexpressed Nurr1 in neural stem cells. 2. Overexpression of Nurr1 could promote the transformation of neural stem cells into dopaminergic neurons( P < 0.05), which was confirmed by immunofluorescence and Western Blot. 3. Transplantation of NNCS can effectively improve the symptoms of rats with Parkinson’s (P < 0.05).4. After transplantation, Nurr1 can promote the transformation of neural stem cells into dopaminergic neurons,greatly improve the survival of transplanted neural stem cells and achieve better therapeutic effect.Conclusion Nurr1 can promote the transformation of neural stem cells into dopaminergic neurons. Transplantation of overexpression of Nurr1 neural stem cells can effectively treat Parkinson’s rats.