基于"祛瘀生肌法"的临床疗效，以及课题组前期研究证实：1）祛瘀生肌中药具有降低β-catenin表达,纠正Wnt信号通路过度激活导致的角质形成细胞增殖与迁移抑制作用(eCAM)；2）角质形成细胞高表达Smad7具有明显拮抗TGFβ信号通路，从而促进细胞增殖与迁移（AJP and Nature Medicine）。本申请围绕"祛瘀生肌法"是否通过Smad7降低β-catenin表达促进创面上皮化这一科学假说，采用两种不同病理模式的糖尿病溃疡模型（链脲佐菌素和db/db），综合ChIP、IP、质粒转染、Luciferase assay、逆转录病毒感染、原位杂交和免疫荧光等方法，通过深入研究祛瘀生肌中药在Smad7和β-catenin及其下游靶基因在角质形成细胞上皮化中作用和调控机制，从而为"祛瘀利于生肌，生肌不致成瘢"的学术观点进一步丰富其科学内涵。

The proposal is based on on the clinical effects of the Tradidional Chiese Medicin methods of "qu-yu-sheng-ji,QYSJ" (removing stasis tissues to stimulate the growth of new skin) on diabetic ulcer, and our published data including 1) QYSJ herbs can increase keratinocyte's migration and proliferation by down-regulating beta-catenin expression (Published in eCAM);2) Smad7 transgenic ketatinocyates have the ability to improve migration and proliferation by countering TGFbeta signaling pathway (Published in AJP and Nature Medicine). This proposal is designed to verify our hypothesis that TCM QYSJ method could regulate beta-catenine through Smad7 to promote wound re-epithelialization.To explore this, we will use two different diabetic mice model(streptozotocin-induced and db/db model, respectively),combined with ChIP, IP, plasmid transfection，luciferase assay, keratinocytes-special adenovirus infection, hybridization in situ and immunofluorescence methods to explore the function of QYSJ herbs in the crosstalk of Smad7 and beta-catenin, and demonstrate the influence of those down-stream target gene in the process of diabetic wound reepithelialization. This study will further enrich our view of"removal of stasis is beneficial for the growth of new tissues with little scar".)