基于代谢组学技术的黄芩-白芍对2型糖尿病模型小鼠的作用机制

Mechanism of Scutellariae Radix-Paeoniae Radix Alba on Mouse Model of Type 2 Diabetes Mellitus Based on Metabolomics Technology

目的:在肾脏代谢组学技术基础上,探讨黄芩-白芍药对对2型糖尿病(T2DM)的防治机制,并通过寻找内源性潜在生物标志物,寻找其相关代谢通路。方法:非糖尿病健康同窝出生仔畜(db/m小鼠)为空白组,同时选择血糖值高于11.1 mol/L的糖尿病瘦素受体基因缺陷(db/db)小鼠进行分组,分为模型组、黄芩-白芍组(5.625 g/kg)、阳性药组(二甲双胍250 mg/kg),给药体积为7.5 mL/kg,1次/d,连续8周,并采用超高效液相色谱与串联四级杆飞行时间质谱仪联用技术(UPLC-Q-TOF-MS/MS)法进行小鼠肾脏代谢组学分析,探寻潜在的生物标志物,联合人类代谢组学数据库(HMDB)和京都基因与基因组百科全书数据库(KEGG)找出相关代谢通路。结果:黄芩-白芍组可改善T2DM模型小鼠代谢轨迹的偏离,同时,寻找出与DN模型及给予黄芩汤干预后具有共同差异的生物标志物14个,涉及8条相关代谢通路,应用相关代谢通路分析方法发现,影响最为广泛的代谢通路可能是甘油磷脂代谢、嘌呤代谢和嘧啶代谢。结论:黄芩-白芍药对治疗T2DM的作用机制可能与其通过调节脂质代谢、能量代谢等多条代谢通路,改善内源性代谢物的水平,恢复机体正常代谢活动有关。

Objective:To investigate the prevention and treatment mechanism of Scutellariae Radix-Paeoniae Radix Alba on type 2 diabetes mellitus(T2DM)and find the relevant metabolic pathways by searching for endogenous potential biomarkers based on renal metabolomics technology.Methods:The non-diabetic healthy young mice born in the same litter(db/m mice)were assigned to the blank group,and the mice deficient in the diabetic leptin receptor gene with a blood glucose value higher than 11.1 mol/L(db/db)were divided into a model group,a Scutellariae Radix-Paeoniae Radix Alba group(5.625 g/kg),and a positive drug group(metformin,250 mg/kg).The drug was administered once per day for eight weeks,with a volume of 7.5 mL/kg,and the ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)method was used for the renal metabolomics analysis of mice to explore the potential biomarkers.The relevant metabolic pathways were identified by combining the human metabolome database(HMDB)and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results:The Scutellariae Radix-Paeoniae Radix Alba group could reduce the metabolic trajectory deviation of T2DM model mice.Meanwhile,14 biomarkers with common differences with DN model and after Huangqin Decoction intervention were identified,involving eight relevant metabolic pathways.Relevant metabolic pathway analysis methods were applied to find that the metabolic pathways with the most extensive influence might be glycerophospholipid metabolism,purine metabolism,and pyrimidine metabolism.Conclusion:The mechanism of Scutellariae Radix-Paeoniae Radix Alba in the treatment of T2DM might be attributed to improving the level of endogenous metabolites and restoring the normal metabolic activities of the body by regulating multiple metabolic pathways such as lipid metabolism and energy metabolism.