增生性瘢痕常发生于烧创伤后，我国发病率高，尚无有效的防治方法。我们发现在瘢痕形成早期抑制血管生成能够抑制瘢痕增生，但瘢痕持续血管化及增生的始动因素还不清楚。我们前期还发现增生性瘢痕中大量巨噬细胞浸润，同时存在Notch信号高表达，抑制Notch信号可以减轻瘢痕增生。由于Notch信号是调节巨噬细胞极化的关键信号，而巨噬细胞可产生多种促血管化及纤维化的关键因子，因此我们提出Notch信号可能通过调控巨噬细胞极化启动瘢痕形成中的血管新生和纤维化。本项目拟收集不同时期的人创面/瘢痕标本，进一步分析Notch信号表达与巨噬细胞极化和瘢痕增生的关系；在巨噬细胞与内皮细胞/成纤维细胞共培养模型中调节Notch信号，及利用巨噬细胞特异性敲除Notch信号的小鼠创面模型，研究Notch信号调控巨噬细胞对瘢痕血管化及纤维化的作用，揭示其分子机制。本研究有望进一步阐明增生性瘢痕的发生机制，为其防治提供新靶点。

Hypertrophic scar form most often at the sites of trama and burns. The disease incidence rate is high in our country and there has been still no effective prevention and treatment methods. We found that the inhibition of angiogenesis at the early phase of wound healing can inhibit the formation of hypertrophic scar, but the initiative factors of continuous vascularization and scar hyperplasia was not clear. We also found that there were a large number of macrophages infiltrating in hypertrophic scar. The high expression of Notch signal Moleculars were also detected and the inhibition of Notch signaling can reduce scar formation. Because the Notch signal is the key signal regulating macrophage polarization, and macrophages can produce various key factors of vascularization and fibrosis, we propose that the Notch signal might initiate the angiogenesis and fibrosis through regulating macrophage polarization. This project aims to collect human wound / scar specimens in different periods of wound healing, and analysis of relationships between the macrophage polarization and scar hyperplasia and the level of Notch signal expression. We also aims to regulate Notch signal in coculture model of macrophages and endothelial cell / fibroblast and to reveal the molecular mechanism use macrophage specific Notch signal knockout mice wound model. This study is expected to further clarify the pathogenesis of hypertrophic scar and to provide a new target for its prevention and treatment.