泽泻益生元对高脂诱导胰岛素抵抗小鼠的作用及其机制研究

Previous studies have shown that prebiotics of Alisma rhizome (AR, polysaccharide of Alisma rhizome) has a significant effect on high fat-induced insulin resistance in obese mice and can significantly regulate and improve the structure of intestinal microflora in mice induced by high fat induction. For further study its mechanism of action, using the intestinal microecology as the pointcut, through the metagenomics-bioinformatics to study the the intestinal microflora structure and functional gene by prebiotics of AR regulation; using metabolomics combine with systems biology analysis to explore the role of prebiotics on intestinal microflora and intestinal microflora marker metabolites, and analysis the intestinal flora (Alisma probiotics) is how to play the role on IR mice. Finally, use of germ-free mice and fecal transplantation to further verify the AR regulation of probiotics can be improved IR mice by the intestinal microecological, and analyze the structure of probiotics in the germ-free mice, to clarify the intrinsic mechanism of microbial structure - functional genomics - metabolomics - Alisma probiotic. Alisma probiotic play a role in improving the overall role of IR, which provides the experimental basis for the clinical application and the development of new drugs for AR. And to provide a methodology for the study and development of traditional Chinese medicine, on improving the IR mice by intestinal microecology, and to provide reference for the development of prebiotics of traditional Chinese medicine.

前期研究表明泽泻益生元(泽泻多糖)对高脂诱导胰岛素抵抗肥胖小鼠的作用显著，并且可以改善由高脂诱导引起的小鼠肠道微生物组结构，为进一步研究其IR改善作用机制，本研究以肠道微生态为切入点，拟采用高通量测序技术，通过宏基因组学-生物信息学探究泽泻益生元对肠道菌群结构组和功能基因组的调控作用；采用微生物代谢组学-系统生物学分析探究泽泻益生元对肠道微生态代谢物的作用，分析泽泻益生元干预后的肠道菌群（益生菌）如何发挥改善IR的作用；最后，拟采用无菌小鼠-泽泻益生元粪便移植法进一步验证泽泻益生菌可以通过肠道微生态改善IR的机制，并分析无菌小鼠益生菌结构组，功能基因组及代谢组，阐明泽泻益生元发挥改善IR整体作用的微生物结构组-功能基因组-代谢组学-益生菌组的内在机制，为泽泻益生元的临床应用和新药开发提供实验基础，为发掘中药通过肠道微生态改善IR的研究开发提供方法学，为中药益生元的开发提供借鉴。

本研究在泽泻益生元(泽泻多糖)的活性筛选和分离纯化及结构鉴定的基础上开展泽泻益生元对高脂诱导胰岛素抵抗肥胖小鼠的作用，以肠道微生态为切入点，通过采用高通量测序技术，通过宏基因组学-生物信息学探究泽泻益生元对肠道菌群结构组和功能基因组的调控作用，结果发现泽泻主要调控拟杆菌门和厚壁菌门，并且调控菌群碳水化合物代谢、短链脂肪酸代谢、胆汁酸等功能基因；采用微生物代谢组学-系统生物学分析探究泽泻益生元对肠道微生态代谢物的作用，进一步分析泽泻益生元干预后的肠道菌群（益生菌）可通过短链脂肪酸代谢、胆汁酸途径发挥改善IR的作用；最后，采用无菌小鼠-泽泻益生元复方粪便移植法进一步验证泽泻益生菌可以通过肠道微生态改善IR的机制，并分析无菌小鼠益生菌结构组及代谢组，阐明泽泻益生元发挥改善IR整体作用的微生物结构组-功能基因组-代谢组学-益生菌组的内在机制，为泽泻益生元的临床应用和新药开发提供实验基础。