microRNAs调控自噬治疗大鼠脊髓损伤的实验研究

Spinal cord injury (SCI) severly impairs human’s health. In order to improve the prognosis of SCI, it is very important to understand its pathogenesis and explore how to reduce and reverse secondary neural damage. Researches have showed that the autophagy is a key factor to regulate neural injury induced by SCI. When injury happens, autophagy has “double-edged sword” effects: proper activation of autophagy is beneficial for neural cells to live under harmful environment; however, overactivation of autophagy may damage neural cells and even cause cell death. Therefore, how to modulate autophagy to act for cell life needs to be further studied. We predicted microRNAs targeted to autophagy related genes Beclin1 and LC3-Ⅱthrough bio-informatics，and found that some of them overlapped with the microRNAs differently expressed betweenSCI and normal spinal cord tissus screened by microRNA chip. We hypothesized that the different expression of microRNAs may be related to the regulation of autophagy in SCI. In this study, we'll try to select and identify microRNAs targeted to Beclin1 and LC3-Ⅱin SCI rat model, and prove that these microRNAs can regulate autophagy in spinal cord injury. Meanwhile, we 'll explore the possibility and feasibility of regulating microRNAs to inhibit rat neural injury induced by SCI, thus provide new targets for clinical treatment of SCI.

脊髓损伤严重威胁人类健康，探索脊髓损伤的发病机制，减轻和逆转继发性神经损伤，对于改善疾病预后具有重要意义。研究发现，自噬在脊髓损伤中起着重要作用。损伤发生后，自噬的适当激活有利于提高神经细胞应对不利环境的能力，但自噬过度激活会造成神经细胞损伤，导致自噬性细胞死亡。因此，如何调控自噬向利于神经细胞存活的方向发展十分重要。我们利用生物信息学技术预测靶向调控自噬关键基因Beclin1及LC3-Ⅱ的miRNAs，发现预测的miRNAs与通过miRNA芯片筛查到的脊髓损伤模型中存在差异表达的miRNAs有重叠。我们推测某些miRNAs的表达变化可能是调控脊髓损伤自噬的重要机制。本课题拟筛选、鉴定大鼠脊髓损伤模型中可能调控自噬基因的miRNAs，证明其在脊髓损伤中对自噬的调控作用。探索应用miRNAs调控自噬治疗脊髓损伤的可能性和可行性，为临床治疗脊髓损伤提供新靶点。