基于调节神经干细胞增殖分化的振荡电场刺激修复脊髓损伤及机制研究

项目名称： 基于调节神经干细胞增殖分化的振荡电场刺激修复脊髓损伤及机制研究

项目编号： No.81471273

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： 钱军

作者单位： 安徽医科大学

项目金额： 70万元

中文摘要： 神经干细胞移植是治疗脊髓损伤的重要手段，但神经干细胞移植存在增殖和分化易受到脊髓微环境干扰的问题。Wnt信号通路对调控干细胞分化及促进神经再生具有重要作用。振荡电场刺激是经临床试验证明有效的修复脊髓损伤的物理方法，可调控Wnt信号通路。本研究采用大鼠脊髓损伤模型，联合应用振荡电场刺激和神经干细胞移植修复损伤脊髓，利用免疫荧光标记、qRT-PCR、Western blot、免疫荧光染色、基因芯片和动物行为学等技术，观察振荡电场刺激对移植的神经干细胞增殖分化和神经再生的调节作用；分析Wnt蛋白的表达及其下游信号通路的激活，探讨在振荡电场刺激下，参与Wnt信号通路调节神经干细胞增殖分化的机制；并进一步研究抑制或增强脊髓内Wnt信号通路对神经再生的影响。以证实振荡电场刺激调节移植的神经干细胞增殖分化和促进神经再生的假说，为联合应用振荡电场刺激和神经干细胞移植修复脊髓损伤提供新的理论依据和技术方向。

中文关键词： 脊髓损伤；Wnt信号通路；振荡电场；神经干细胞

英文摘要： Neural stem cell transplantation increases the hope for treatment of spinal cord injury, but it still exists a problem that the proliferation and differentiation of neural stem cell is interfered by the microenvironment in the injured spinal cord. A single neural stem cell transplantation can not meet the need for treatment of spinal cord injury. It has shown that the proliferation and differentiation of neural stem cell is promoted by the Wnt signaling pathway in previous studies. The electrical field stimulation is an effective physical method for the treatment of spinal cord injury proved by clinical trials, and it can activate the Wnt signaling pathway in the microenvironment of spinal cord. On this basis, the purpose of this project is to repair the injured spinal cord in rats by combining oscillating field stimulation and neural stem cell transplantation. Observing the proliferation and differentiation of exogenous neural stem cell by immunofluorescence labeling technology ; detecting the expression and distribution of Wnt signaling pathway protein in the injured spinal cord by qRT-PCR and Western blot ; observing the regeneration of axons and myelin by tissue staining and electron microscope technology; evaluating the functional recovery via BBB score and neurophysiological test. Exploring the mechanism of inducing the proliferation and differentiation of neural stem cells and promoting neurons regeneration by oscillating field stimulation; confirming the hypothesis that the oscillating electric field stimulation can promote the proliferation and differentiation of neural stem cell; Providing a theoretical basis and a new direction for the treatment of spinal cord injury by means of oscillating electric field and neural stem cell transplantation.

英文关键词： Spinal cord injury;Wnt signaling;Oscillating electrical field;Neural stem cells