目的 以虚寒大鼠为模型，观察吴茱萸汤对模型大鼠血清代谢谱的影响，探讨其治疗虚寒呕吐证可能的内在作用机制。方法 采用复合法（大黄+顺铂）制备虚寒呕吐模型。通过超高液相色谱-质谱（UPLC-MS）技术非靶向获取虚寒呕吐大鼠血清的高通量代谢组数据，结合多元变量分析和数据库检索，对不同组别大鼠血清中内源性代谢物进行分析，筛选鉴定出潜在的差异代谢物，并通过Metabo Analyst软件进行代谢通路分析。结果 血清代谢谱对照组和模型组完全分离，吴茱萸汤给药组靠近对照组，表明从机体内源性物质变化的水平模型复制成功，且吴茱萸汤在一定程度上能够干预大鼠的虚寒呕吐症状，提示吴茱萸汤干预后机体具有恢复到正常状态的趋势。对筛选出来的35种差异性代谢物进行通路分析，发现虚寒呕吐证的机制可能与体内脂代谢、氨基酸代谢通路异常相关，且吴茱萸汤对其通路可能具有调控作用；网络模块化分析发现7个模块之间关系密切，焦谷氨酸、花生四烯酸、5-羟基色胺、异柠檬酸、三酰甘油等生物靶点可作为虚寒呕吐证的生物标志物。结论 吴茱萸汤能够改善虚寒呕吐模型的生理特征，机制可能与吴茱萸汤调节虚寒呕吐大鼠体内紊乱的氨基酸代谢、能量代谢、脂代谢等异常有关。

Objective To observe the effect of Wuzhuyu Decoction on the serum metabolic profile of the model rats with deficiency cold, and explore its possible mechanism for treating deficiency cold and vomiting syndrome. Methods A rat model of deficiency cold and vomiting was prepared by a composite method (Rhei Radix et Rhizoma + cisplatin). The high-throughput metabolome data of the serum of rats with deficiency-cold and vomiting was obtained by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS), and multivariate analysis combinated with database retrieval was used to analyzed the endogenous metabolites in rat serum from different groups and discover differential metabolites. Besides, metabolites were analyzed by Metabo Analyst software for possible metabolic pathways. Results The serum metabolic spectrum of control group and model group were completely separated. The Wuzhuyu Decoction group was close to the control group, indicating that the horizontal model of endogenous material changes was successfully replicated, and Wuzhuyu Decoction could interfere with the symptoms of deficiency cold and vomiting in rats, suggesting that the rat body had a tendency to return to normal state. In total, modular analysis of 35 serum differential metabolites, and deficiency cold and vomiting syndrome was related to abnormal lipid metabolism and amino acid metabolism pathways and Wuzhuyu Decoction may have a regulatory effect on its pathways; Metabolites revealed close relationship among seven modules; Pyroglutamic acid, arachidonic acid, serotonin, isocitric acid, triglyceride and other biological targets can thus be used as biomarkers of deficiency cold and vomiting. Conclusion Wuzhuyu Decoction can improve the physiological characteristics of the model of deficiency-cold and vomiting. The mechanism may be related to the regulation of abnormal amino acid metabolism, energy metabolism, and lipid metabolism in rats with deficiency-cold vomiting.

R285.5;R285.61

国家自然科学基金面上项目（81274112）；国家自然科学基金面上项目（81373986）；国家自然科学基金面上项目（81473372）