慢性炎症是糖尿病皮肤溃疡持续难愈的重要原因之一，炎症微环境影响细胞的增殖与迁移。本研究基于前期发现：1）尽管部分“虚瘀夹杂”证候糖尿病溃疡创面TGFβ阴性表达，但其下游炎症相关因子（pSmad2、NF-κB）却为阳性表达。2）基因芯片数据库显示祛瘀生肌中药上调糖尿病溃疡创面Follistatin蛋白，且与细胞迁移功能相关的基因表达亦增强。本申请围绕祛瘀生肌中药可能“通过Follistatin/Activin/Smads信号通路改善糖尿病溃疡炎症微环境”的科学假说，利用db/db糖尿病小鼠溃疡模型平台，综合运用重组人源蛋白、原位杂交、流式细胞检测和免疫荧光技术，以及特定基因敲除、转基因小鼠细胞体外培养等方法，通过深入研究祛瘀生肌中药对Follistatin/Activin及其下游靶基因在创伤愈合过程中的时序干预，丰富“祛瘀利于生肌，生肌不致成瘢”学术观点的科学内涵，有利推动该法在临床的运用。

Chronic inflammation is one of the main causes of the refractory healing in diabetic ulcer. Inflammation microenvironment, which influences the proliferation and immigration of cells, has been a focus of the recent research. Based on the final reports of the previous Youth Fund, which discovers that: 1)Although some TGFβ is negative around the diabetic ulcer wound in some clinical “deficiency mixed up with stasis” syndrome patients, its downstream related inflammatory factors including pSmad2、NF-κB is positive. 2) Gene chip database shows that Chinese medicine which removes stasis and promotes granulation can up-regulate Follistatin protein around the diabetic ulcer wound and the gene expression which is related to cell immigration and adhesion will be up regulated. This application centers on the scientific hypothesis that the inflammation microenvironment of the diabetic ulcer is ameliorated via the Follistatin/Activin/Smads signaling pathway. We will use db/db diabetic ulcer mice model platform, exogenous recombinant human protein, in situ hybridization, immunofluorescence and specific gene knockout/transgen mouse keratinocyte cultured in vitro to study the time-series intervention of Chinese medicine which removes stasis and promotes granulation on the Follistatin/Activin and its downstream target genes during the process of wound healing. The purpose of this study is to enrich the scientific connotation that removing stasis is beneficial to promoting granulation and promoted granulation won’t lead to hypertrophic scar.