NGF 上调 miRNA-132 促脊髓损伤修复的机制研究

NGF gene modified neural stem cells transplantation plays an important role in the treatment of spinal cord injury, but the mechanism of treatment is still lack of in-depth study. Our previous study found that NGF gene modified neural stem cell protective effect on spinal cord injury; also observed the difference of CREB, miRNA-132 expression after spinal cord injury; proposes NGF gene modified neural stem cells transplantation through sustained expression of nerve growth factor, promote the phosphorylation of CREB and promote the expression of miRNA-132 and promote the regeneration of the injured spinal cord axons. We intend to use the behavior evaluation, magnetic resonance imaging, electrophysiological, immunohistochemical and gene chip, protein electrophoresis and molecular biology method to observe the migration and differentiation of transplanted cells in vivo after transplantation and gene expression, to investigate the NGF gene modified neural stem cell transplantation can promote the repair mechanism of spinal cord injury. The completion of this study will be helpful to elucidate the molecular mechanism of NGF gene modified neural stem cells transplantation for spinal cord injury, and to provide new ideas for the treatment of spinal cord injury.

NGF基因修饰神经干细胞移植在脊髓损伤的治疗中起重要作用，但治疗机制尚缺乏深入研究。我们前期研究发现NGF基因修饰神经干细胞对损伤脊髓的保护效应；也观察到脊髓损伤后CREB、miRNA-132表达的差异；据此提出NGF基因修饰神经干细胞移植通过持续表达神经生长因子，促进CREB的磷酸化，进而促进miRNA-132的表达而促使受损脊髓神经轴突的再生。我们拟采用行为学评估、磁共振成像、神经电生理、免疫组化及基因芯片、蛋白质双向电泳等分子生物学方法观察移植细胞在体内的迁移、分化和移植后基因表达差异，探讨NGF基因修饰神经干细胞移植促进脊髓损伤的修复机制。本研究的完成将有利于阐明NGF基因修饰神经干细胞移植治疗脊髓损伤的分子机制，并将为脊髓损伤的治疗策略提供新的思路。