低频脉冲电磁场调控microRNAs表达促进少突胶质前体细胞分化在脊髓损伤修复中的作用及机制研究

The low frequency pulsed electromagnetic is a effective therapies for spinal cord injury, but the mechanism is not clear. It has shown that the differentiation of oligodendroglia precursor cells is closely related to the repair of spinal cord injury. Moreover, the differentiation of oligodendroglia precursor cells is promoted by miR-219 and miR-338.In our study, a low frequency pulsed electromagnetic field was designed to repair spinal cord injury in rats. Overexpression of miR-219, miR-338 and miR-322 in oligodendroglia precursor cells by the stimulation of low frequency pulsed electromagnetic field is shown in vitro.In addition, the differentiation of oligodendroglia precursor cells is promoted by the stimulation of low frequency pulsed electromagnetic field in vivo.In conclusion,the low frequency pulsed electromagnetic field may promote the differentiation of oligodendroglia precursor cells results from the overexpression of miR-219, miR-338 and miR-322 and repair spinal cord injury further. On this basis, the purpose of this project is to Observe the proliferation and differentiation of oligodendroglia precursor cells by the stimulation of low frequency pulsed electromagnetic field, explore the mechanism of differentiation of oligodendroglia precursor cells promoted by miR-219, miR-338 and miR-322 in low frequency pulsed electromagnetic field , evaluate the functional recovery of spinal cord injury rats,clarify the role and mechanism of differentiation of oligodendroglia precursor cells in spinal cord injury rats by stimulation of low frequency pulsed electromagnetic field and provid a theoretical basis for low frequency pulsed electromagnetic field applied to clinical finally.

低频脉冲电磁场已被证实可修复脊髓损伤，但机制不清。少突胶质前体细胞分化与脊髓损伤修复密切相关，而miR-219和miR-338可促进少突胶质前体细胞分化。我们前期设计了可修复大鼠脊髓损伤的低频脉冲电磁场，该电磁场可上调体外少突胶质前体细胞中miR-219、miR-338和miR-322 表达，促进脊髓损伤大鼠少突胶质前体细胞分化，提示电磁场可能通过上调miR-219、miR-338和miR-322表达促进少突胶质前体细胞分化，进而修复脊髓损伤。本课题拟通过体外和体内实验，观察低频脉冲电磁场对少突胶质前体细胞增殖和分化的影响，探讨电磁场调控miR-219、miR-338和miR-322表达促进少突胶质前体细胞分化的机制，并基于miRNA调控靶基因观察电磁场对大鼠脊髓损伤的修复，从而阐明低频脉冲电磁场促进少突胶质前体细胞分化在脊髓损伤修复中的作用及机制，为低频脉冲电磁场的临床应用提供理论依据。

脊髓损伤是一种常见的中枢神经系统创伤，寻找新的、有效的治疗方式，并探索其治疗机制，有着重要的科学和社会意义。低频脉冲电磁场作为一种无痛、无创且安全性很高的神经电生理刺激技术已被证实可用于修复脊髓损伤，但机制不清楚。本研究设计了可修复大鼠脊髓损伤的低频脉冲电磁场，该低频脉冲电磁场可通过促进少突胶质前体细胞向少突胶质细胞分化和髓鞘再生，以及抑炎作用和促神经营养作用，促进脊髓损伤大鼠神经功能的恢复。为了进一步研究低频脉冲电磁场促进少突胶质前体细胞分化的机制，我们研究发现：在体外培养的少突胶质前体细胞中，低频脉冲电磁场上调靶向Lingo1的miR-219-5p表达，促进少突胶质前体细胞分化。本项目初步阐明了低频脉冲电磁场促进少突胶质前体细胞分化在脊髓损伤修复中的作用及机制，为低频脉冲电磁场的临床应用提供了理论依据。