我们前期研究发现，川崎病时存在明显的血管内皮损伤和功能的异常，炎症介质可能影响血管内皮祖细胞的分化行为而影响川崎病冠状动脉损伤和修复。生理条件下，Notch4信号在调控血管内皮祖细胞的分化发育中起关键作用，但在川崎病冠状动脉损伤中，Notch4信号是否调控血管内皮祖细胞损伤尚不清楚。我们通过建立免疫性冠状动脉损伤小鼠模型，研究血管内皮祖细胞损伤的发生；并观察不同时间冠状动脉内皮细胞Notch4信号的表达特点，研究Notch4信号活化的时空特性；取血管内皮祖细胞培养，观察血管内皮祖细胞的增殖分化，且予细胞转染RNAi技术抑制Notch4基因，研究Notch4信号对血管内皮祖细胞增殖分化的调控作用；此外对免疫性冠状动脉损伤小鼠予γ-分泌酶抑制剂干预，探讨抑制Notch4信号活化是否能改善冠状动脉血管内皮细胞损伤,从细胞分化角度进一步阐明血管内皮祖细胞对损伤血管内皮的修复机制。

Our previous study found that there were significant vascular endothelial injury and dysfunction in Kawasaki disease. The inflammatory mediators may affect the differentiation of endothelial progenitor cells, which affect coronary artery injury and repair. Under physiological conditions, the signal of Notch4 plays a key role in the regulation of endothelial progenitor cells differentiation and development, but it is unclear whether Notch4 signal regulates the damage of vascular endothelial progenitor cell in Kawasaki disease. Through the establishment of immune coronary artery injury model, we study the expression of Notch4 signal at different times, the spatial and temporal characteristics of Notch4 signal activation on coronary artery endothelial cells, the proliferation and differentiation of endothelial progenitor cells using cultured endothelial progenitor cells, and the regulating effect of Notch4 signal on proliferation and differentiation of endothelial progenitor cells by cells transfection RNAi technology inhibiting the Notch4 gene. Also we study whether it can improve coronary artery endothelial cell injury to inhibit Notch4 signal activation by γ-secretase inhibitors in immune coronary artery injury model, and clarify the repair mechanisms of injured vascular endothelial from the perspective of vascular endothelial progenitor cells differentiation.