Epo/EpoR信号通路促进大鼠脊髓损伤后再髓鞘化的实验研究及机制的初步探讨

Demyelination following spinal cord injury (SCI) is one of the important reasons for the loss of spinal cord function, endogenous neural stem cells in spinal cord (NSCs) can spontaneously remyelination, but new myelin is very slim and inadequate, if can remyelinate the remaining continuous nerve tissue effectively will get the greatest extent the functional recovery of spinal cord. Erythropoietin (Epo) can significantly promote the recovery of nerve function after SCI , its anti-inflammatory and anti apoptosis and other environmental improvement have been found in previous research work that Epo/EpoR signal pathway can promote the differentiation of endogenous NSCs in the adult spinal cord to oligodendrocytes, but the final remyelination the degree of improvement and the corresponding mechanism has not been reported in the literature.We design to activate Epo/EpoR signaling pathway following SCI and analyze the expression of downstream signal molecule of Epo/EpoR signaling pathway, myelinating oligodendrocytes, new myelin degree and remyelination of pathway of many indicators on multilevel, describing mechanism of Epo/EpoR signaling pathway to promote oligodendrocyte differentiation and exploring Epo/EpoR signal pathway on myelination effect and its mechanism after SCI.

脊髓损伤(SCI)后的脱髓鞘改变是脊髓神经功能丧失的重要原因之一，脊髓内源性神经干细胞(NSCs）虽然可以自发进行进行再髓鞘化，但新生的髓鞘非常纤薄且不充分，如果能有效的对残存连续神经组织进行再髓鞘化将能够最大程度的恢复脊髓功能。促红细胞生成素（Epo）能够明显促进SCI神经功能恢复，其抗炎、抗凋亡及改善内环境等多种作用机制相继被发现，课题组在前期的工作中发现Epo/EpoR信号通路能够促进成体脊髓内源性NSCs向少突胶质细胞分化，但最终再髓鞘化改善的程度及其相应的作用机制尚且没有文献报道。本课题设计在SCI后激活Epo/EpoR信号通路，通过分析Epo/EpoR下游信号分子的表达、髓鞘化少突胶质细胞、新生髓鞘程度及与再髓鞘化有关信号通路表达等多个指标的多层面分析，明确Epo/EpoR信号通路促进少突胶质细质细分化的机制，探讨Epo/EpoR信号通路对SCI后再髓鞘化的作用及其机制。

脊髓损伤(SCI)后的脱髓鞘改变是脊髓神经功能丧失的重要原因之一，脊髓内源性神经干细胞(NSCs）虽然可以自发进行进行再髓鞘化，但新生的髓鞘非常纤薄且不充分，如果能有效的对残存连续神经组织进行再髓鞘化将能够最大程度的恢复脊髓功能。促红细胞生成素（Epo）能够明显促进SCI神经功能恢复，其促进自噬、抗炎、抗凋亡及改善内环境等多种作用机制相继被发现，课题组在前期的工作中发现Epo/EpoR信号通路能够促进成体脊髓内源性NSCs向少突胶质细胞分化，并促进神经细胞自噬，减轻脊髓的损伤，但其改善的程度及其相应的作用机制尚且没有文献报道。本课题设计在SCI后激活Epo/EpoR信号通路，通过分析Epo/EpoR下游信号分子的表达、神经细胞自噬、髓鞘化少突胶质细胞、新生髓鞘程度、再髓鞘化有关信号通路表达等多个指标的多层面分析，通过体外实验及SCI动物模型，明确Epo/EpoR信号通路促进少突胶质细质细分化的机制，探讨了Epo/EpoR信号通路对SCI后再髓鞘化与自噬的作用及其机制。