背根神经节前体细胞移植对马尾神经综合征鞍区感觉障碍功能修复重建的实验研究

项目名称： 背根神经节前体细胞移植对马尾神经综合征鞍区感觉障碍功能修复重建的实验研究

项目编号： No.30872613

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 史建刚

作者单位： 中国人民解放军第二军医大学

项目金额： 26万元

中文摘要： 本研究旨在探讨马尾神经损害机制并探索应用新生大鼠背根神经节干细胞移植修复马尾神经功能的可能性，同时观察了氢生理盐水在大鼠急性马尾神经损害中的抗氧化应激、抑制神经元凋亡及神经保护作用等方面的作用。实验结果表明：1.大鼠马尾神经压迫损伤可以导致逆行性脊髓相应部位出现凋亡。在这个过程中，PUMA是一个关键的调控基因，其作用机制可能是通过p53通路促进细胞凋亡；而SirT2可能的作用是负向调节p53，从而抑制PUMA的表达。2.新生大鼠背根神经节干细胞可以进行分离和培养，并且在体外主要分化为少突胶质细胞。通过蛛网膜下腔显微注射的方法将分离获得的神经干细胞移植入受损马尾神经周围的脑脊液中，这些细胞可存活至一周以后而且全部分化为少突胶质细胞。但由于存活时间较短，这些细胞尚未形成髓鞘，所以未对宿主大鼠的相关功能起到明显的改善作用。3.氢生理盐水对氧化应激反应具有抑制作用,减少了神经纤维变性及神经元凋亡，且对神经损害具有保护作用,这些作用与甲强龙类似。这些结果提示脑脊液内注射神经干细胞可以通过分化成为少突胶质细胞进而形成髓鞘，并最终可能修复马尾神经的功能，这为临床马尾神经损害防治提供了新的思路和途径。

中文关键词： 马尾神经损害；背根神经节干细胞；移植；神经功能修复

英文摘要： In this study, we investigated the mechanisms underlying injury of cauda equina and determined the role of transplanting neural stem cells from neonate dorsal root ganglion (DRG) in repairing injury of cauda equina. Meanwhile, we observed the effect of hydrogen saline on oxidative stress, neuronal apoptosis and neuroprotection during the pathological process of injury of cauda equina. Results are listed as followed: 1) Cauda equina compression led to retrograde apoptosis in correlated parts of the spinal cord in rats. During this process, PUMA is one of the key regulatory genes, which may act through P53 pathway and then promote neuronal apoptosis. While SirT2 plays a negaitive regulation on P53 pathways to inhibit PUMA expression. 2) We found that neural stem cells could be isolated from neonate DRG and cultured in vitro successfully, and then differentiated into oligodendrocytes. After separated, the neural stem cells were transplanted into the cerebrospinal fluid around injured cauda equina by intrathecal microinjection. We found these cells could survive for a week, and all of them differentiated into oligodendrocytes. However, the survival time is too short for the cells to form myelin, so the transplant has little effect on functional recovery of host rats. 3) Hydrogen saline inhibited oxidative stress, reduced both nerve fibrae degeneration and neuronal apoptosis, and protected the nerves from damage, with a similar effect to methylprednisolone. This study indicate that intrathecal transplanting neural stem cells can repair cauda equina for function recovery, which is possibly mediated by their differentiation into oligodendrocytes to form myelin, providing new insight into clinical prevention and treatment of injury of cauda equina.

英文关键词： injury of cauda equina; DRG neural stem cells; transplant; neural functional recovery