目的 采用代谢组学技术观察附子Aconiti Lateralis Radix Praeparata对小鼠血清内源性代谢物的影响，寻找其相关生物标志物和可能表征附子临床治疗作用的代谢途径及相关靶点，探讨其发挥疗效的分子机制。方法 将20只雄性小鼠随机分为2组，分别ig附子水煎液和蒸馏水，小鼠给药量为15 mL/（kg·d），连续ig 4 d；采集各组血样，利用UPLC-MS/MS技术进行分析，主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）等分析方法进行数据模式识别，并根据变异权重系数（VIP）大于1和手动积分计算筛选出差异代谢物；利用差异代谢物进行通路分析；运用Cytoscape和MetScape对差异代谢物进行网络模块化分析并筛选靶标。结果 通过数据模式识别，附子组与对照组均能完全分离；共筛选出18个差异代谢物，其含量都呈上调趋势；通过通路分析，得出5条相关通路，分别为亚油酸代谢、花生四烯酸代谢、淀粉和蔗糖代谢、烟酸和烟酰胺代谢和磷酸肌醇代谢通路；网络模块化分析共得到14个模块，其中最大的2个模块是花生四烯酸代谢通路和亚油酸代谢通路；在整个网络中，花生四烯酸（59）、亚油酸（55）、烟酰胺（26）和棕榈酸（11）节点度值大于均值（8.010），涉及的通路分别为花生四烯酸代谢、亚油酸代谢、烟酸和烟酰胺代谢和饱和脂肪酸β-氧化通路；共筛选出26个相关基因，同属于细胞色素P450（CYP450）酶系。结论 附子可能通过作用于CYP450，影响花生四烯酸代谢等途径，进而调节机体能量代谢，从而发挥临床治疗作用。

Objective To observe the effects of Aconitum carmichaelii on serum metabolites in mice by metabolomics technology, and to explore biomarkers and metabolic pathways and targets related to its treatment of various ailments such as cardiovascular diseases, in order to uncover its molecular mechanism of efficacy. Methods Twenty male mice were randomly divided into two groups, and A. carmichaelii decoction and distilled water were orally administered with the dose of 15 mL/(kg·d) for consecutive 4 d respectively. Collected blood samples of each group were analyzed using UPLC-MS/MS technology, and data pattern recognition was performed using PCA, PLS-DA and other analytical methods. Meanwhile, differential metabolites were screened out based on VIP greater than 1 and manual integral calculation. The differential metabolites were used for pathway analysis. Network modular analysis and targets screening were performed by Cytoscape and MetScape. Results When performing data pattern recognition, the aconite group and the control group could be completely separated. A total of 18 differential metabolites were screened out, and their contents were up-regulated. Pathway analysis was performed to obtain five related pathways, namely linoleic acid metabolism, arachidonic acid metabolism, starch and sucrose metabolism, nicotinate and nicotinamide metabolism, and inositol phosphate metabolism. Fourteen modules were obtained using the network analysis, the largest two of which were arachidonic acid metabolism pathway and linoleic acid metabolism pathway. The degree of arachidonic acid (59), linoleic acid (55), nicotinamide (26), and palmitic acid (11) were greater than the mean value (8.010) in the network, and the related pathways were arachidonic acid metabolism, linoleic acid metabolism, nicotinate and nicotinamide metabolism, and saturated fatty acid beta-oxidation pathway respectively. A total of 26 genes were screened out, all of which belonged to the cytochrome P450 enzyme system. Conclusion A. carmichaelii may affect arachidonic acid metabolism by acting on CYP450, thereby improving the body's energy metabolism and producing therapeutic effects.

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国家自然科学基金面上项目（81873024，81773923，81473372，81373986）；国家自然科学基金青年项目（81903819）；北京市自然科学基金项目（7202143）；中国中医科学院传承项目（KT18002ZX）