利用代谢组学方法鉴定泽泻对高脂饲料诱导的高脂血症治疗的尿液生物标示物和阐明生物化学作用机制。超高压液相色谱和质谱联用测定对照组、高脂血症模型组及泽泻提取物治疗组尿液,采用偏最小二乘判别分析法研究对照组、高脂血症模型组及泽泻提取物治疗组之间的代谢物谱差异,鉴定了14个生物标示物,高脂血症模型组高脂饲料上调了大鼠尿液硬脂酸酰胺、油酸酰胺、3-甲基尿苷、十六烷酰胺、吲哚-3-甲酸和肌酐,同时下调了二十四碳六烯酸、3-氧-甲基多巴、吲哚-3-甲酸葡糖苷酸、多巴胺、尿酸、苯丙氨酸、左旋肉碱和甲基肌苷。泽泻提取物逆转了这些异常上调和下调的生物标示物。泽泻提取物改善了由高脂饲料造成的异常的脂肪酸代谢、氨基酸代谢和嘌呤代谢。代谢组学技术能够应用于高脂血症及其泽泻对其治疗的生物化学作用研究。
The identified biomarkers and biochemical mechanism of therapeutic effect of Alisma orientale on diet-induced hyperlipidemia rats was studied by metabolomic approach. Urinary from control,hyperlipidemia and Alisma orientale treatment groups was analyzed by ultra performance liquid chromatography coupled with mass spectrometry. Acquired data were subjected to PLS-DA for differentiating the control,hyperlipidemia and Alisma orientale treatment groups. Biomarkers were identified by PLS-DA. Fourteen metabolites were identified as potential biomarkers. Compared with control rats,up-regulated octadecanamide,oleamide,3-methyluridine,palmitic amide,indole-3-carboxylic acid and creatinine as well as down-regulated tetracosahexaenoic acid,3-O-methyldopa,3-indole carboxylic acid glucuronide,dopamine,uric acid,phenylalanine,L-carnitine and methylinosine were observed in diet-induced hyperlipidemia group. The up-regulation and down-regulation of metabolites were reversed by treatment with Alisma orientale. The perturbations of fatty acid metabo-lism,amino acid metabolism and purine metabolism were observed in diet-induced hyperlipidemia rats. The study shows that metabonomics could be applied to investigation of identified biomarkers and biochemical mechanism of therapeutic effect of Alisma orientale on diet-induced hyperlipidemia rats.