NSCs、BMSCs移植治疗锰中毒大鼠多巴胺能神经损伤分子机制研究

项目名称： NSCs、BMSCs移植治疗锰中毒大鼠多巴胺能神经损伤分子机制研究

项目编号： No.81472933

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 闫永建

作者单位： 山东省医学科学院

项目金额： 60万元

中文摘要： 多巴胺能神经细胞损伤是引起锰中毒及帕金森氏病（PD）的主要病理机制之一。本研究拟通过人胚胎干细胞（hES）诱导分化的神经干细胞(NSCs )和骨髓间充质干细胞(BMSCs)移植治疗大鼠锰中毒模型，观察干细胞移植对锰中毒神经损伤的治疗作用，探讨α-Synuclein、neurofilaments、ubiquitin proteins及TH在锰中毒引起的多巴胺能神经元损伤中的作用及分子机制。本课题主要研究内容：将NSCs和BMSCs移植入锰中毒大鼠体内，观察其治疗作用，通过分析多巴胺能神经细胞形态及功能，证实移植干细胞在大鼠体内分化为TH+神经元，并保护和/或刺激宿主损伤的多巴胺神经元再生；对比分析大鼠多巴胺能神经元的基因表达谱改变。通过以上研究寻找锰中毒引起多巴胺能神经元表型及功能改变的关键基因与信号通路，为干细胞移植治疗锰中毒的临床应用提供实验研究基础。

中文关键词： 锰中毒；神经干细胞；骨髓间充质干细胞；α-突触核蛋白；多巴胺神经元

英文摘要： The main pathological mechanism of manganese poisoning and Parkinson's disease(PD) is dopaminergic nerve cells' damages. In this study, we intends to transplant human neural stem cells(NSCs) which are induced and differentiated from human embryonic stem cells(hES) and bone marrow mesenchymal stem cells (BMSCs) to manganese poisoning rats. Observe the therapeutical effects of stem cell transplantation as well as investigate the role and molecular mechanism of α-Synuclein、neurofilaments、ubiquitin proteins and Tyrosine Hydroxylase(TH) in dopaminergic neuron injury induced by manganese poisoning through these experiments. The major contents of this research are as follows. Transplant NSCs and BMSCs to rats in order to investigate their therapeutical effects. Demonstrate that transplanted stem cells can differentiate normally into Tyrosine Hydroxylase positive neuron and protect and/or stimulate the regeneration of host's injured dopaminergic neurons by analyzing of dopaminergic neural cells' morphology and function. Comparatively analyse changes of gene expression profile of dopaminergic neurons to estimate and verify possible susceptible genes of manganese poisoning' rats. Through the above study, search for key genes and signal passways of dopaminergic neurons' phenotypic and functional changes so as to provide the trial basis for the clinical use of transplanting stem cells to treat manganese poisoning

英文关键词： Manganese poisoning;Neural stem cell;Bone marrow stem cell;α-synuclein;Dopamine neurons