前期研究表明，肠组织中的CBS(胱硫醚-β-合酶，cystathionine-β-synthase)-H2S信号随溃疡性结肠炎的进展而下调，小分子化合物fraxinellone能逆转这一过程并展现出良好的治疗效应。以fraxinellone为探针，首次发现其结合蛋白AMPK（磷酸腺苷激活的蛋白激酶）可能是H2S分子合成酶CBS的上游调控因子。本项目拟进一步考察AMPK-CBS-H2S信号在结肠炎组织局部各细胞及体外培养的肠上皮细胞-T细胞体系中的分布及其变化情况。通过对AMPK与CBS分子的三维立体结构的计算和单/多位点突变后AMPK与CBS的结合试验考察分子间相互作用。阐明fraxinellone如何影响AMPK-CBS分子间信号传递及炎性肠病过程中的分子变化。构建多个炎性肠病模型，着重考察给予fraxinellone上调内源性H2S的下游效应及其对疾病治疗的作用和意义。

It has been shown in preliminary studies that CBS (cystathionine-β-synthase)- H2S signal was down-regulated with the progress of ulcerative colitis. And fraxinellone, a small molecule from TCM Dictamni, demonstrated significant effects on the inflammatory bowel disease through reversing the decline of H2S in the local colonic tissue. We found for the first time that AMPK (adenosine mono-phosphate-activated protein kinase), a target protein of fraxinellone, might be the upstream regulatory factor of H2S synthase - CBS. In this project we intend (1) to investigate the distribution and variation of AMPK-CBS-H2S signal both in colon tissue and in the in vitro culture system of colonic epithelial cell - T cell, (2) to measure the intermolecular interactions between AMPK and CBS by the calculation of three-dimensional structure of the molecules and the binding assays of the proteins as well as their single / multi-sites mutations, and (3) to examine the effects of fraxinellone on AMPK-CBS interaction and variation in the process inflammatory bowel disease. Finally, several models of inflammatory bowel disease will be set up to study the downstream pathway and effects of endogenous H2S upregulation by fraxinellone.