基于代谢组学方法探索葛根芩连汤方剂治疗2型糖尿病大鼠的效果研究

Exploration of treated with Gegen Qinlian decoction prescription on type 2 diabetic rats based on metabolomics

目的运用代谢组学的分析方法探索葛根芩连汤方剂治疗2型糖尿病大鼠的效果,包括模式轮廓比较、生物标志物筛查与代谢通路推断等。方法将健康雄性SD大鼠分为3组,依次为正常对照组、2型糖尿病模型组和葛根芩连汤(8. 2 g/kg)治疗组;除正常组外,其余各组大鼠均给予高脂饲料并联合链脲佐菌素以确立2型糖尿病疾病模型。随后连续灌胃给药3周,并于末次给药后12小时内收集大鼠尿液样本;运用HPLC/MS-IT-TOF手段进行高分辨质谱检测,同时应用OPLS-DA多元模式手段以比较各组大鼠尿液的代谢轮廓差异以及潜在的生物标志物,并推断其可能影响到的代谢通路。结果本研究共筛查出15个生物标志物,包括多肽氨基酸类物质、磷酯类物质、核苷酸类物质以及其它类物质;涉及的代谢通路主要为嘌呤代谢。结论 2型糖尿病的疾病发生与嘌呤代谢存在着紧密的联系,尤其是核苷酸类物质作为其中的关键作用靶点;葛根芩连汤通过多靶点调节嘌呤代谢异常以至于整个机体内部的疾病紊乱状态,从而促使其转归为正常水平。

Objective Metabolomics analysis was used to explore the effect of Gegen Qinlian decoction on type 2 diabetic rats,including comparison of pattern contours,biomarker screening and metabolic pathway inference.Methods Healthy SD male rats were divided into three groups,normal control group,type 2 diabetic model group and(8.2 g/kg)with Gegen Qinlian decoction treatment group.In addition to the normal group,all the rats were administrated a high-fat feed with streptozotocin,to establish the animal model of type 2 diabetes.After building model with continuous lavage for three weeks,the urine sample were extracted after 12h after the last lavage.And using HPLC/MS-IT-TOF method to characterize the urine metabolic differences of each group,with orthogonality multivariate statistical analysis were used to screen potential biomarkers,and inferred the possible metabolic pathways.Results In this study,a total of screening out 15 biomarkers,including polypeptide amino acids,phospholipids,nucleotides,and other substances,the metabolic pathways involved are mainly purine metabolism.Conclusion The occurrence of type 2 diabetes were closely related with purine metabolism,especially the nucleotides as a key target.Gegen Qinlian decoction regulates purine metabolic abnormalities and even causes a state of disease disorder throughout the body through multiple targets,thereby prompting its return to normal levels.