目的:基于代谢组学技术阐明清络通痹方中配伍生地黄和三七对雷公藤的减毒作用。方法:建立基于高效液相-线性离子阱-静电场轨道杂交质谱(HPLC-LTQ-Orbitrap-MS)的代谢组学分析测定方法,测定各组大鼠血浆和肝脏中内源性代谢小分子的变化。建立正交偏最小二乘-判别分析(OPLS-DA)模型进行模式识别,通过比较各组生物样本观测值在OPLS-DA模型得分图上的距离,判断生地黄和三七对整方的贡献。并通过单因素方差分析筛选差异性化合物,阐明配伍药物生地黄和三七可能调控的代谢通路。结果:OPLS-DA得分图结果显示,雷公藤+生地黄组大鼠的生物样本观测值在整体上距离清络通痹方较近,提示清络通痹方中生地黄的作用明显。单因素方差分析筛选出差异化合物,清络通痹方中的生地黄调整了肝脏中的甘氨胆酸、牛磺酸以及溶血性磷脂酰胆碱(16∶0)等代谢物水平从而发挥了配伍减毒的作用,而清络通痹方中的三七则调整了肝脏中的硫胺素和溶血性磷脂酰胆碱(16∶0)水平从而发挥配伍减毒的作用。结论:初步阐明了整方基于中医“异类相制”理论配伍用药的合理性和科学性。 OBJECTIVE: To elucidate the attenuating effect of Radix Rehmanniae Preparata and Radix Notoginseng on Tripterygium wilfordii based on metabolomics techniques. Methods: A metabolomic analysis method based on HPLC-LTQ-Orbitrap-MS was established for the determination of endogenous small molecules in the plasma and liver of rats Variety. Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) model was established for pattern recognition. By comparing the observed distance of each group of biological samples with the score of OPLS-DA model, the contribution of Dioscorea and Panax notoginseng . One-way ANOVA was used to screen the differential compounds, and the metabolic pathways that Radix Rehmanniae Preparata and Panax notoginseng could regulate were elucidated. Results: The results of OPLS-DA score chart showed that the biological samples from the Tripterygium wilfordii + Radix Rehmanniae group were closer to Qinglutongbi than those from Qingluotongbi, suggesting that Radix Rehmanniae Preparata has a significant effect on Rehmannia glutinosa. One-way analysis of variance (ANOVA) was used to screen out the different compounds. Rehmanniae of Qingluotongbi Formula adjusted the levels of glycocholic acid, taurine and hemolytic phosphatidylcholine (16:0) in liver, Compatibility of attenuated role, while the Qingluo Tongbi Fang 37 in the liver is adjusted by the thiamine and hemolytic phosphatidylcholine (16: 0) level to play the role of compatibility attenuated. Conclusion: The rationality and scientificness of the whole prescription based on the theory of traditional Chinese medicine “heterogeneous phase system” are preliminarily clarified.