论文部分内容阅读
目的观察酪氨酸羟化酶(tyrosine hydroxylase,TH)和孤儿核受体相关因子1(nuclear receptor related factor1,Nurr1)基因修饰的骨髓间充质干细胞(MSCs)移植治疗帕金森病(PD)大鼠的有效性,验证并评价Nurr1对TH所起的调控作用,探寻TH在特定环境中适量表达的调控机制。方法将稳定转染TH、TH-Nurrl的和未经转染的MSCs分别移植至PD大鼠后运用旋转试验观测PD大鼠的行为学变化。移植后第9周应用免疫组织化学和Western blot检测移植治疗后TH的表达情况。结果基因修饰组PD大鼠行为学较MSCs组明显改善(P<0.05),且TH-Nurr1组动物行为改善和TH抗原阳性率均高于TH组(P<0.05)。结论基因修饰的MSCs移植后能高效稳定地表达TH,且双基因的协同表达将极大提高PD基因治疗的效果,从而为PD治疗的基因选择提供新的依据和思路。
Objective To observe the effects of tyrosine hydroxylase (TH) and nuclear receptor related factor 1 (Nurr1) gene modified bone marrow mesenchymal stem cells (MSCs) transplantation on the treatment of Parkinson’s disease To verify and evaluate the regulatory effect of Nurr1 on TH and to explore the regulatory mechanism of TH in moderate environment. Methods The MSCs transfected with TH, TH-Nurrl and untransfected MSCs were respectively transplanted into PD rats. Rotation test was used to observe the behavioral changes of PD rats. At 9 weeks after transplantation, the expression of TH was detected by immunohistochemistry and Western blot after transplantation. Results The behavior of genetically modified rats was significantly improved compared with that of MSCs (P <0.05). The animal behavior improvement and TH antigen positive rate in TH-Nurr1 group were higher than that in TH group (P <0.05). Conclusion The genetically modified MSCs can express TH with high efficiency and stability after transplanted, and the synergistic expression of the two genes will greatly enhance the effect of PD gene therapy, which will provide a new basis and ideas for the gene selection of PD treatment.