MicroRNA-222和MicroRNA-338双慢病毒序贯表达系统协同促进神经损伤修复的作用及机理研究

应用多种手段都可不同程度地促进损伤神经的再生，但新生轴突髓鞘化程度较低，主要是由于新生施万细胞（SCs）形成的髓鞘细薄，最终影响再生神经传导功能的恢复。前期实验研究表明，miRNA-222能够促进SCs增殖，miRNA338有助于SCs形成髓鞘。据此，我们提出这样的假设：在损伤神经修复过程中，序贯表达两个调控基因miRNA-222和miRNA-338，即损伤初期先表达miRNA-222促进SCs增殖，加速Büngner带形成，引导轴突的延伸；经过特定的时间窗再表达miRNA-338调控SCs的髓鞘化因子，促进新生神经轴突的髓鞘化。本项目在进一步完善体外细胞学实验基础上，拟在大鼠体内坐骨神经损伤模型中采用双慢病毒系统调控miRNA-222及miRNA-338序贯表达，评估其对损伤坐骨神经修复的协同促进作用，并进一步阐明miRNA-222和miRNA-338协同促进坐骨神经损伤修复的作用机理。

Application of a variety of means could promote regeneration of injured sciatic nerve for different degrees, but new nerve fibers generally have low myelinations, and ultimately affect recovery of nerve function. Preliminary experimental research showed that, miRNA-222 could promote the proliferation of Schwann cells (SCs), miRNA338 helped SCs form myelin sheath. Accordingly, we propose the assumption that in the repair of peripheral nerve injury, the sequential expression of miRNA-222 and miRNA-338 should be regulated. The initial expression of miRNA-222 promotes SCS proliferation, accelerating the formation of Büngner band, to guide and promote axonal extension; expression of miRNA-338 in the repairing period can regulate myelination factor of SCs, and promote new axonal myelination. In the base of improving the in vitro experiments, this project aims to further adopt in vivo sciatic nerve injury model of rats, using double lentiviral system to regulate miRNA-222 and miRNA-338 sequential expression, and assess the synergistic effect on the sciatic nerve injury. And on this basis to further elucidate synergistic effect mechanism of miRNA-222 and miRNA-338 on repairing of sciatic nerve injury.