基于UPLC-Q-TOF-MS分析雷公藤配伍甘草治疗肾病综合征大鼠的尿液代谢组学

目的:考察雷公藤配伍甘草对肾病综合征大鼠尿液中内源性代谢产物的影响,通过尿液代谢组学技术探讨该药对的作用机制。方法:大鼠随机分为4组,分别为空白组、模型组、雷公藤单独给药组(TPW组)和雷公藤配伍甘草给药组(TPW-GLY组)。采用UPLC-Q-TOF-MS,结合主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA),对尿液样品的代谢物图谱进行模式识别及生物标记物的筛选与鉴定。结果:空白组,模型组,TPW组及TPW-GLY组的代谢轮廓有明显差异,筛选并鉴定出空白组与模型组间具有显著性差异的生物标记物29个,其中受TPW-GLY组回调的生物标记物14个,受TPW组回调的生物标记物11个;TPW-GLY组和TPW组显著差异物7个,分别为N-乙酰谷氨酸,二羟基粪甾烷酸,烟尿酸,12-酮脱氧胆酸,甘油三酯(16∶0/16∶0/20∶4),泛醌Q2和1,3,7-三甲基尿酸。结论:雷公藤与甘草配伍给药后,可能通过改善肾病综合征大鼠体内的氨基酸代谢、胆汁酸代谢、脂肪及脂肪酸代谢、能量代谢及嘌呤代谢等过程,改善了疾病状态,进而起到减毒增效的作用。

Analysis of Urine Metabonomics of Nephrotic Syndrome Rats Treated with Compatibility of Tripterygii Wilfordii Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Based on UPLC-Q-TOF-MS

Objective: To investigate the changes of endogenous metabolites in urine of nephrotic syndrome rats treated by compatibility of Tripterygii Wilfordii Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma,and to explore its mechanism by urine metabonomics. Method: Rats were randomly divided into 4 groups,including the blank group,the model group,the Tripterygii Wilfordii Radix et Rhizoma (TPW) group and the compatibility of Tripterygii Wilfordii Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma (TPW-GLY) group.All urine samples were determined by UPLC-Q-TOF-MS.Data was analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Result: The urine metabolite profiles in 4 groups were separated obviously.Twenty-nine biomarkers with significant difference were identified between the blank group and the model group,and 14 biomarkers were recovered by the administration of TPW-GLY,and 11 biomarkers were recovered by the administration of TPW.There were 7 biomarkers between TPW group and TPW-GLY group as N-acetylglutamic acid,dihydroxycoprostanoic acid,nicotinuric acid,triglyceride(16:0/16:0/20:4),12-ketodeoxycholic acid,ubiquinone Q2,1,3,7-trimethyluric acid. Conclusion: After compatibility with Glycyrrhizae Radix et Rhizoma,Tripterygii Wilfordii Radix et Rhizoma may take effect on nephrotic syndrome rats through the regulation of amino acid metabolism,bile acid metabolism,fatty acid and fat metabolism,energy metabolism,purine metabolism and other processes.