振荡电场刺激对脊髓少突胶质前体细胞分化的影响及机制研究

Myelin integrity is important for normal physiological function of axon which is surrounded by myelin. Spinal cord injury often accompanied by varying degrees of myelin damage, how to promote the myelin regeneration, make naked axon regaining myelin sheath surrounding, become the key to the repair of spinal cord injury. Myelin sheath, which is formed by oligodendrocytes outburst by Oligodendrocyte progenitor cells (OPCs), adenosine can promote OPCs differentiation by adenosine receptors. Our preliminary animal experiments have showed that OFS can stimulate myelination regeneration by promoting OPCs differentiation. However, the role of OPCs differentiation and related signaling molecules receptors involved was not well studied. In this project, by establishing animal and cellular model of spinal cord injury treated with OFS, differentiation and maturation characteristics of OPCs in remyelination, the content, activity and distribution changes of adenosine A2B receptor in differentiation of OPCs are studied. In this way the project will benefit new understanding of mechanism of OFS in enhancing remyelination after spinal cord injury.

髓鞘的完整性是保证其包裹的轴突具备正常生理功能的前提，脊髓损伤常存在不同程度的髓鞘损伤。如何促进髓鞘再生，使其重新包绕轴突，促进脊髓功能恢复，成为脊髓损伤修复的关键。髓鞘由少突胶质细胞形成，后者由少突胶质前体细胞（OPCs）分化而来，神经元分泌的腺苷可通过腺苷受体促进OPCs分化。本课题组前期利用振荡电场刺激器治疗脊髓损伤大鼠，发现振荡电场可促进脊髓损伤修复，其机制与加速OPCs分化促进髓鞘再生相关，但具体作用方式和潜在分子机制尚未阐明。本项目综合利用细胞和动物模型，聚焦振荡电场对OPCs分化规律的影响和作用方式（直接和/或间接），探索腺苷A2B受体的表达、活性及分布在振荡电场促进髓鞘再生中的作用。本项目探索振荡电场促进髓鞘再生治疗脊髓损伤的分子机制，为促进脊髓损伤的临床治疗和振荡电场刺激器临床应用提供理论和实验依据。

振荡电场刺激（OFS）器每隔15分钟变换电场的极性，通过周期变换方向的输出电流，对损伤脊髓组织进行双向交替电场刺激，可同时促进脊髓损伤处双向生长。脊髓损伤常存在不同程度髓鞘损伤，髓鞘再生的过程对于保护新生轴突及恢复神经冲动跳跃式传导十分重要。髓鞘再生的细胞基础是成熟少突胶质细胞，其由少突胶质前体细胞（OPCs）分化成熟而来，因此研究OFS对OPCs及髓鞘再生的影响具有重要意义。本项目主要包括三个研究内容：（1）振荡电场刺激器的研制；（2）研究振荡电场刺激对 OPCs 分化的影响；（3）研究振荡电场刺激在脊髓损伤后髓鞘再生中的作用。本项目综合考虑刺激器的功能性、可植入性、生物相容性等因素，研制了以原电池供电、输出电流为38.1 μA、振荡周期为30分钟、硅橡胶封装的植入式振荡电场刺激器。完成的动物实验表明，植入式振荡电场刺激器具有良好的生物相容性，振荡电场刺激可以促进大鼠脊髓损伤后轴突再生，减少瘢痕形成，促进运动功能恢复，促进髓鞘再生及电生理功能的改进，并探讨了少突胶质前体细胞在其中的作用。本研究为电场刺激治疗脊髓损伤提供了新的方法及理论基础。