采用超高效液相色谱串联四级杆飞行时间质谱(UPLC/Q-TOF-MS)联用技术,通过非靶向代谢组学方法分析大鼠尿液内源性代谢物的变化,研究藜芦妨害人参发挥药效作用的机制。建立脾气虚大鼠模型,连续给药15天,测定力竭游泳时间及血液中白细胞、红细胞、血红蛋白的含量。结果表明,人参可显著提高脾气虚模型大鼠的力竭游泳时间(p〈0.01),升高白细胞、红细胞及血红蛋白含量(p〈0.05,p〈0.01),藜芦对脾气虚模型大鼠各项指标无明显影响(p〉0.05),人参与藜芦配伍后对脾气虚模型大鼠各项指标均无显著影响(p〉0.05),表明藜芦妨害了人参发挥药效作用。采用UPLC/Q-TOF-MS技术及非靶向代谢组学的方法分析了空白组、模型组、人参组、藜芦组、参藜组对脾气虚模型大鼠的尿液代谢组差异,其中主成分分析(PCA)得分图显示各组代谢轮廓有显著差别,并通过正交偏最小二乘法-判别分析(OPLS-DA)及数据库检索,鉴定出15种人参干预调节脾气虚模型大鼠的潜在生物标志物,从中找出了7种人参藜芦配伍后减弱人参上述干预作用的潜在生物标志物,并对其涉及的代谢通路进行了系统分析。上述研究结果表明,人参藜芦配伍后妨害了人参对脾气虚模型大鼠的治疗作用,其机理可能是影响人参对体内能量代谢、免疫平衡及氧化还原反应等相关代谢的调节。
A urinary untargeted metabonomics method based on UPLC / Q-TOF-MS was established to investigate the mechanism of compatibility of Panax ginseng and Veratrum nigrum in Spleen qi deficiency rat.Spleen qi deficiency rat model was established,then the exhaustive swimming time and the content of white blood cells,red blood cell and hemoglobin in the blood was detected after administration for 15 days. The results showed that Panax ginseng could increase the exhaustion swimming time(p0. 01)and the content of white blood cells,red blood cell and hemoglobin in the blood(p 0. 05,p 0. 01)of spleen qi deficiency rats,and Veratrum nigrum or compatible application had no significant effect index mentioned above(p0. 05). The urinary metabolic profiling was analyzed by using UPLC / Q-TOF-MS and the obtained data were analyzed by PCA. The score of PCA showed that there was significant difference among the metabolic profile of different groups. According to the results of OPLS-DA and the databases,fifteen potential biomarkers were identified as the therapeutic effect of Panax ginseng,and seven of them and their pathways were considered as reducing the therapeutic effect of Panax ginseng by co-administration with Veratrum nigrum. The results indicated that the effect of Panax ginseng on promoting energy metabolism,regulating immune and antioxidation in the spleen qi deficiency rats were decreased after the compatibility of Panax ginseng and Veratrum nigrum.