联合移植过表达Nurr1基因的神经干细胞与小胶质细胞治疗帕金森病大鼠模型

既往研究证实应用神经干细胞（NSCs）移植治疗帕金森病（PD）有一定疗效。然而，由于忽视了局部微环境，导致移植NSCs存活、定植等出现困难，故难以获得长期稳定的疗效。研究表明，Nurr1基因在微环境中小胶质细胞活化的调控及NSCs向DA神经元分化中起关键作用。因此，我们认为过表达Nurr1的NSCs与小胶质细胞的联合移植可抑制微环境中小胶质细胞的活化和炎症因子的产生，同时促进其分泌神经营养因子，从而为移植NSCs提供良好的微环境，促进其存活、定植并分化成多巴胺能（DA）神经元。在本研究中，我们将首先通过体外实验研究过表达Nurr1以及与小胶质细胞共培养对NSCs存活、分化的影响；然后将过表达Nurr1的NSCs和小胶质细胞联合移植入PD大鼠纹状体，进一步明确Nurr1基因以及微环境中小胶质细胞对移植NSCs存活、定植和向DA神经元分化的重要调控作用，为NSCs移植治疗PD提供新的治疗靶点。

Previous studies have demonstrated that application of neural stem cells (NSCs) transplantation in the treatment of Parkinson's disease ( PD ) have certain curative effect. However, because of the neglect of the microenvironment, transplanted NSCs can hardly survive and colonize, so it is difficult to obtain the long-term efficacy and stability. Researches indicate that the Nurr1 gene plays a key role in the regulation of activation of microglial cell in the microenvironment and doparminergic differentiation of NSCs. Therefore, we assume that co-transplatation of Nurr1 gene modified NSCs and microglial cells can inhibit the activation of microglial cells and the production of inflammatory factors, and promote the secretion of neurotrophic factors at the same time, so as to provide a perfect microenvironment for transplanted NSCs, promote the survival, colonization and dopaminergic differentiation of NSCs. In this study, we will first explore the effects of over expression of Nurr1 and co-culture with microglia on the survival and differentiation of NSCs by in vitro study; then we will explore the therapeutic effect of co-transplantation of Nurr1 gene modified NSCs and microglial cells in PD rat models, to further clarify the important role of Nurr1 gene and microglial cells of the microenvironment in the survival, colonization and dopaminergic differentiation of transplanted NSCs, which will provide new therapeutic targets for NSCs transplantation in the treatment of PD.