目的 比较《金匮要略》中酸枣仁汤（Suanzaoren Decoction，SZRD）和酸枣汤（Suanzao Decoction，SZD）的物质基础和抗失眠、抗焦虑药效差异。方法 基于超高效液相色谱-三重四极杆-线性离子阱质谱（Ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry，UPLC-Qtrap-MS）技术定量测定SZRD和SZD中20种化学成分作为评价指标并明确汤液煎煮方法；同时采用超高效液相色谱-轨道阱串联质谱（Ultra-high performance liquid chromatography-orbitrap tandem mass spectrometry，UPLC-Orbitrap-MS/MS）技术鉴定和比较二者的化学成分；以对氯苯丙氨酸（p-chlorophenylalanine，PCPA）诱导的失眠模型小鼠评价和比较二者的抗失眠、抗焦虑药效。结果 用陶瓷岩涂层铁锅以600 W功率煎煮酸枣仁25 min，再加入其余药材煎煮40 min的煎煮条件能够较好地符合《金匮要略》原文记载。在酸枣仁和酸枣全果用量均为汉代2升的情况下，SZRD中酸枣仁皂苷A/B、斯皮诺素、6'''-阿魏酰斯皮诺素、木兰花碱、茯苓酸、藁本内酯的含量是SZD的6倍以上，SZD中甘草素、异甘草苷、异甘草素、知母皂苷AIII的含量是SZRD的2倍以上。2种汤液质谱检测信号最强的前100个成分中有42个成分含量在SZD中含量较高，21个成分在SZRD中含量较高。差异成分中还鉴定出3个异喹啉生物碱［(-)-异延胡索单酚碱、碎叶紫堇碱、巴婆碱］、1个吡咯烷生物碱（水苏碱）和1个甾体生物碱（浙贝宁），其中SZD中碎叶紫堇碱和巴婆碱的相对含量分别是SZRD的5.2和4.8倍，SZD中(-)-异延胡索单酚碱、水苏碱、浙贝宁的相对含量分别是SZRD中的0.3、0.4和0.4倍。2种汤液在PCPA诱导的失眠模型小鼠中表现出相似的抗失眠和抗焦虑作用，药效差异不显著。结论 按照《金匮要略》原文记载煎煮的SZRD和SZD物质基础差异显著，在特定条件下二者相似的抗失眠、抗焦虑药效是多种活性成分共同作用的结果。

Objective Compare the differences in material basis and anti-insomnia and anti-anxiety efficacy between Suanzaoren Decoction (SZRD, 酸枣仁汤) and Suanzao Decoction (SZD, 酸枣汤) in the Jin Gui Yao Lue. Methods This study quantifies 20 chemical ingredients as evaluation indicators to establish the boiling methods of SZRD and SZD, based on ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry (UPLC-Qtrap-MS) technology. Moreover, the ultra-high performance liquid chromatography-orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) metabolite identification method specific to the Chinese herbal medicine was used to identify and compare the chemical profile of the two decoctions. Lastly, the p-chlorophenylalanine (PCPA) induced insomnia model mice were used to evaluate and compare the efficacy of the two decoctions in anti-insomnia and anti-anxiety. Results The method of boiling Suanzaoren in ceramic-coated iron pot for 25 min and adding other herbs then continuing to boil for 40 min can match well with the original records in Jin Gui Yao Lue. When Suanzaoren and Suanzao fruit were both used with the amount of 2 litters in Han Dynasty, the contents of jujuboside A, jujuboside B, spinosin, 6‴-feruloylspinosin, magnoflorine, pachymic acid and ligustilide in SZRD were over 6-fold higher than those in SZD, whereas the contents of liquiritigenin, isoliquiritin, isoliquiritigenin and timosaponin AIII in SZD were over 2 times than those in SZRD. Among the top 100 compounds with the strongest mass spectrometric signals detected in the two decoctions, 42 compounds exhibited higher contents in SZD and 21 compounds were enriched in SZRD. Among the differential compounds, three isoquinoline alkaloids [(-)-isocorypalmine, cheilanthifoline and asimilobine], one pyrrolidine alkaloid (stachydrine) and one steroidal alkaloid (zhebeinine) were further identified. The relative abundances of cheilanthifoline and asimilobine in SZD were 5.2 times and 4.8 times higher than those in SZRD, respectively; meanwhile, the relative abundances of (-)-isocorypalmine, stachydrine and zhebeinine in SZD only reached 0.3, 0.4 and 0.4 times the corresponding values in SZRD. The anti-insomnia and anti-anxiety efficacies of the two decoctions in the PCPA induced insomnia mice are similar to each other, and no statistically significant intergroup difference in their pharmacological efficacy was observed.. Conclusion Under the original decoction method recorded in Jin Gui Yao Lue, SZRD and SZD show significant differences in material basis, yet their similar anti-insomnia and anti-anxiety effects under specific condition may result from the combined actions of multiple active components.

R283.6

国家重点研发计划项目（2025YFC3509100）；国家自然科学基金项目（U24A20787）；陕西省科技厅重点研发计划项目（2024SF-YBXM-520）；陕西省教育厅重点科学研究计划项目（23JY025）；陕西省中医药管理局科研项目（2021-GJ-JC001）；秦创原中医药产业创新聚集区项目（L2024-QCY-ZYYJJQ-X209）<