肠道菌群紊乱与2型糖尿病关系密切，可影响胰岛素抵抗通路信号水平并引起代谢网络变化。苦参味苦性寒，具有清热燥湿的功效。在前期研究表明苦参能够明显减轻高糖诱导糖尿病大鼠胰岛素抵抗状态、抑制蛋白非酶糖基化改善糖尿病微循环的基础上，本项目依据中医糖尿病清热燥湿治法，结合现代医学最新认识，从肠道菌群-内毒素-慢性炎症致病网络、胰岛素抵抗信号通路和代谢网络调控三个层次探讨苦参抗糖尿病物质基础及作用机制。构建T2DM动物模型，以苦参主要成分为干预手段，进一步开展苦参抗糖尿病药效学评价，结合UPLC-MSn技术从内、外源代谢组调控水平找到其治疗糖尿病的实验依据；采用宏基因组学考察给药后肠道菌群的结构变化，采用分子生物学技术发现活性成分对内毒素及相关因子、特异性炎症因子、胰岛素抵抗信号通路的调节作用，阐明苦参成分通过多靶点协同发挥抗糖尿病的作用机制，为中药抗糖尿病研究提供思路与方法学参考。

Recent studies have shown that type 2 diabetes is directly associated with intestinal dysbacteria. Chinese herbs “KuShen” which can clear away heat and dry dampness. Based on our preliminary studies which indicate the Sophora flavescens Ait. could improve high glucose-induced T2DM insulin resistance and inhibit non-enzymatic protein glycation end product formation, and according to traditional Chinese medicine therapeutic method of “Qingre and Zaoshi” and modern medicine theory about type 2 diabetes , this project will establish T2DM animals for evaluating the improvement of insulin resistance of Sophora flavescens Ait.. A metabonomic approach based on UPLC-MSn will be developed to characterize the serum/urine/faeces metabolic profiles associated with insulin resistance and investigate the intervention mechanisms of Sophora flavescens Ait.. Meanwhile, applied by metagenomics technique, species-level structural changes of gut microbiota mediated by Sophora flavescens Ait. will be resolved in a microbiome wide association study strategy. To determine the expression of LPS and related factors, specific inflammatory cytokines, insulin signaling pathway related cytokines or gene, protein and to study their internal relations. The implement of this subject will elucidate mechanism of improving insulin resistance in type 2 diabetes mellitus and therapeutic material basis of Sophora flavescens, and provide new research methods and ideas for other Chinese Traditional Medicine.