从“菌-毒-炎-糖”致病途径探讨2型糖尿病肠道湿热证证候特点及葛根芩连汤干预机制

中医药治疗2型糖尿病肠道湿热证疗效确切，但证候特点和防治机制尚不明确。近年来研究发现，肠道菌群失调、内毒素释放增加、慢性炎症与2型糖尿病密切相关。课题组前期研究也表明，2型糖尿病肠道湿热证人群经中药治疗后，肠道Faecali和Bifido两种有益菌明显增加，α1-酸性糖蛋白炎症水平降低，脂联素水平升高，且变化均与糖化血红蛋白、空腹血糖呈显著相关。由此，我们认为“菌-毒-炎-糖”致病网络可能是2型糖尿病肠道湿热证的病理基础及中医药防治机制所在。本项目采用人群研究结合动物实验，以葛根芩连汤为干预手段，通过元基因组学、分子免疫、生物信息学等技术，研究2型糖尿病肠道湿热证特征性菌群谱、内毒素及相关因子、特异性炎症因子、胰岛素抵抗信号通路等及其内在相关性，探讨2型糖尿病肠道湿热证证候特点和干预机制。通过本项目的示范性研究，为阐释中医证候的科学内涵提供新视角，为2型糖尿病的中医药防治提供新思路。

The treatment for type 2 diabetes of intestinal damp and heat syndrome with traditional Chinese medicine（TCM） has obtained good curative effects, but the characteristics of the syndrome and prevention mechanism are not yet clear. Recent studies have shown that type 2 diabetes is directly associated with intestinal dysbacteria, the release of LPS and the chronic inflammation. Our previous researches also have suggested that after treated by Chinese herbal medicine, faecalbibacterium and bifidobacterium, two species of intestinal positive bacteria, exhibited a significant increase together with a decrease of α1-AGP and an increase of adiponectin. What`s more, the changes were substantially related to glycosylated hemoglobin and fasting blood glucose. Based on these findings,we believe that,the pathogenic network ,“Intestinal microbiota-LPS-Inflammation-insulin resistance”, may be the pathogenesis of type 2 diabetes of intestinal damp and heat syndrome,but also the mechanism of TCM in treatment of type 2 diabetes. Carrying out a human population study combined with animal experiments and taking Gegen Qinlian decoction as intervention to study the characteristic flora spectrum of type 2 diabetes of intestinal damp and heat syndrome, LPS and related factors, specific inflammatory cytokines, insulin signaling pathway and their internal relations, the study aims at investigating the character of type 2 diabetes of intestinal damp and heat syndrome and its intervention mechanism by using metagenome, molecular immunology, bioinformatics and other cutting-edge technologies. Through a demonstration research on intestinal damp and heat syndrome,we hope to provide a fresh perspective to illustrate the scientific connotation of TCM symptoms and a novel idea for the TCM prevention and treatment of type 2 diabetes.