miRNA-126/SDF-1/CXCR7通路在内皮祖细胞移植促进卒中后血管新生中的作用机制研究

移植内皮祖细胞能够促进血管新生和神经再生，但移植的内皮祖细胞在缺血微环境中迁移能力弱、存活率低。目前研究发现miRNAs可通过转录后水平调控蛋白，影响干细胞迁移和存活。我们前期研究提示基质细胞衍生因子SDF-1能够促进缺血性卒中后内皮祖细胞迁移能力和存活率，这可能与miR-126直接调控SDF-1的表达有关，但其调控机制尚不明确。本项目将以大鼠大脑中动脉栓塞为模型，应用miRNA修饰内皮祖细胞这一新方法，研究1）miR-126在内皮祖细胞中对SDF-1的调控作用，明确其对内皮祖细胞迁移和存活能力的影响；2）miR-126对SDF-1及其受体CXCR7和CXCR4的调节作用；3）利用miR-126基因修饰的内皮祖细胞治疗缺血性卒中，研究基因修饰提高内皮祖细胞自身在缺血区的存活的同时，是否能促进内源性神经祖细胞和内皮祖细胞的迁移和存活的能力。本项目的成功将为临床干细胞移植治疗卒中提供理论基础。

Endothelial progenitor cells（EPCs）transplantation was a promising treatment for angiogenesis and neurogenesis, while the engrafted EPCs had poor migration and survival rate. The present study found that miRNAs can regulate protein expression post-transcriptionally then effect stem cell migration and survival. Our previous study indicated that stromal derived factor (SDF-1) could promote EPC migration and survivability, this maybe related with miR-126 which could directly regulate SDF-1, while little is known about the mechanisms. This project will use rat middle cerebral artery occlusion model, to study 1）how miR-126 regulate SDF-1 and how miR-126 influence EPC migration and survival rate; 2）the underlying mechanisms of miR-126 on SDF-1 and its receptors CXCR7 and CXCR4；3）if EPC modified with miR-126 which was transplanted into a rat model of ischemic stroke could promote the transplanted and endogenous stem cell migration and survival. This research will provide the theoretical basis for clinical stem cell-based therapy in stroke.