血管新生障碍是糖尿病伤口愈合困难的关键病因。我们的前期研究表明，2型糖尿病小鼠皮肤伤口愈合减慢，表达Ang-1降低，内皮祖细胞（EPCs）功能降低，而硫化氢（H2S）可加速其皮肤伤口愈合，且作用与改善糖尿病EPCs功能有关。但尚不清楚H2S改善EPCs功能和伤口愈合的分子机制。本研究拟通过观察经H2S或H2S+Ang-1抑制剂治疗后糖尿病小鼠皮肤伤口愈合情况和皮肤Ang-1/Tie2通路信号蛋白表达的体内研究，和Ang-1抑制剂、siRNA 沉默Ang-1后，H2S对EPCs功能影响的改变和EPCs Tie2受体后信号蛋白表达变化的体外研究，以及小鼠EPC的Mitragel Plug血管新生体内研究，阐明EPCs 的Ang-1/Tie2信号通路在介导H2S促血管新生和伤口愈合中的作用机制，有望为糖尿病足溃疡的治疗寻找新靶点，为H2S在糖尿病下肢血管病变和足溃疡中的临床应用奠定科学基础。

Diabetic foot ulceration is still a serious and intractable clinical issue, and the dysfunction of angiogenesis is a key reason of refractory wound healing in diabetic population.Our preliminary study revealed that there were delayed skin wound heaing course,decreased Ang-1 expression in skin tissue and deficient tube formation and adhesion function of EPC in db/db diabetic mice; and hydrogen sulfide(H2S)treatment accelerated their skin wound closure rate.This effect of H2S was related to the restoration of endothelial progenitor cell(EPCs) angiogenic function. However, it is not clear that what is the detailed mechanism of the improvement of EPC functions stimulating by H2S. In the present study,we will answer this scientific question by observing the wound healing course and the Ang-1/Tie2 signaling protein expression change in wound skin tissue through the in vivo study in db/db diabetic mice treated with H2S, H2S+Ang-1 inhibitor, or observing the angiogenic function alteration and the Tie2 post-receptor signaling protein change of EPCs by the in vitro study in diabetic EPCs treated with H2S+/- Ang-1 inhibitor or si-Ang-1,and the in vivo angiogenic study of Mitragel plug after injection of different EPCs into C57BL/6 mice, to elucidate the detailed mechanism of Ang-1/Tie 2 signaling in mediating the pro-angiogenic effect of H2S in diabetes. This optimal work will provide a potential therapeutic target for diabetic foot ulceration, and provide the scientific basis for the future clinical application of H2S in the occlusive artery disease and wound healing of lower extremities in diabetic populations.