铁过载损伤机制及Hmox1基因的条件控制表达技术在脑出血后神经干细胞移植中的研究

项目名称： 铁过载损伤机制及Hmox1基因的条件控制表达技术在脑出血后神经干细胞移植中的研究

项目编号： No.81471176

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： 卞留贯

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 神经干细胞（NSC）移植对于脑出血后的神经功能重建具有改善作用。然而，血肿分解产生的神经毒性物质- - 高浓度铁离子可能是影响移植NSC在体存活的主要因素，极大限制了NSC移植在脑出血急性期的应用、且影响最终的治疗效果。目前铁过载代谢状态下的神经干细胞损伤机制尚不清楚，本研究拟结合前期铁过载引起神经干细胞损伤的初步发现，1）验证铁离子诱导体外NSC损伤过程中关键调控分子Hmox1的功能；2）阐明Hmox1对铁代谢相关通路的调控，对在离体铁过载模型中NSC存活的影响；3）在体脑出血模型中，探索药物诱导调控技术抑制Hmox1表达以此促进NSC增殖分化、改善神经功能。本课题的研究将提示关于脑出血后移植NSC的铁过载损伤机制，促进神经干细胞移植的转化应用，并为出血性脑血管病神经功能的重建提供一条崭新的思路。

中文关键词： 神经干细胞；脑出血

英文摘要： Transplantation of neural stem cell (NSC) can improve neurological functions after intracerebral hemorrhage. However, iron, one of the toxins relieved by clot, may play a main role in transplanted NSC injury and destabilizing the application of NSC transplantation in acute phase, which may impede the treatment. However, the mechanism of NSC injury caused by iron overload remains unclear. In this study combined with previous result showing the iron-induced NSC injury ex vivo, we will explore that: 1) the evidence of Hmox1 functioning as a key regulator in NSC injury induced by iron in vitro; 2) clarifying the pathway of Hmox1 involving the iron metabolism; 3) In intracerebral hemorrhage model, the possibility of conditional inhibiting Hmox1 as to improve stem cell proliferation, differentiation and neurological function recovery as well. This research will indicate the potential mechanism of NSC transplantation iron overload after intracerebral hemorrhage, prompt some new information of NSC transplantation in intracerebral hemorrhage, and provide some novel idea for the treatment of hemorrhagic cerebrovascular disease.

英文关键词： neural stem cell;intracerebral hemorrhage