目的 基于代谢组学技术，通过小鼠血清内源性代谢物的变化寻找吴茱萸发挥生物效应的代谢途径和有关靶点，研究吴茱萸发挥疗效的分子机制。方法 小鼠随机分为对照组和吴茱萸组，给予吴茱萸进行干预，采用超高效液相色谱串联质谱（UPLC-MS/MS）技术分析2组小鼠血样，采用主成分分析、偏最小二乘判别分析、正交偏最小二乘判别分析等方法，筛选差异代谢物并进行代谢通路分析；使用Cytoscape及Metscape软件对差异代谢物进行网络模块化分析，筛选可能的作用靶点。结果 数据模式识别显示吴茱萸组与对照组血清样本完全分离；共获得13个差异表达代谢物；通路分析共获得4条通路；网络模块化分析共获得11个模块，其中花生四烯酸代谢通路和亚油酸代谢通路是最大的2个模块；在整个模块中，烟酰胺、花生四烯酸、棕榈酸、亚油酸节点度均大于均值，涉及的通路包括烟酸和烟酰胺代谢、花生四烯酸代谢、亚油酸代谢及饱和脂肪酸β-氧化；通过筛选获得细胞色素P450（cytochrome P450，CYP450）酶系相关的26个基因。结论 吴茱萸可能通过作用于CYP450酶系，影响花生四烯酸、亚油酸、烟酸和烟酰胺等代谢途径，调控机体能量代谢，进而实现生物效应。

Objective To explore the pathways and targets evoked by Wuzhuyu (Euodia rutaecarpa) as well as the molecular mechanism related to its biological effect through the changes of endogenous metabolites. Methods Mice were randomly divided into control group and E. rutaecarpa group, E. rutaecarpa was given to intervene. The blood samples of two groups were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The analysis methods such as principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis were selected to identify data patterns. Differential metabolites were screened according to VIP > 1 and manual integral calculation, and then the metabolic pathways analysis was performed. Cytoscape and Metascape software were used to establish the network modularization analysis of differential metabolites and screen possible targets. Results The result of data pattern recognition showed that serum sample of E. rutaecarpa group was completely separated from control group and 13 differential expressed metabolites were obtained. Fout pathways were found by pathway analysis. Network modular analysis obtained 11 modules in total, among which arachidonic acid and linoleic acid metabolic pathway were the two largest modules. In the whole module, the node degrees of nicotinamide, arachidonic acid, palmitic acid and linoleic acid were all greater than the mean. The pathways involved nicotinic acid and nicotinamide metabolism, arachidonic acid metabolism, linoleic acid metabolism and saturated fatty acid β-oxidation. A total of 26 genes were screened out, all of which were belong to cytochrome P450 enzyme system. Conclusion E. rutaecarpa may regulate energy metabolism and affect metabolic pathways of arachidonic acid, linoleic acid, nicotinic acid and nicotinamide by acting on cytochrome P450 enzymes to achieve biological effect.

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国家自然科学基金面上项目（81873024）；国家自然科学基金青年项目（81903819）；北京市自然科学基金资助项目（7202143）；中国中医科学院传承项目（KT18002ZX）