目的 比较正常和抗生素大鼠对酸枣仁总黄酮体内代谢转化反应的差异，及2组大鼠血浆中斯皮诺素的药动学变化特征。方法 采用ig联合抗生素建立抗生素干预大鼠模型；正常与抗生素大鼠ig酸枣仁总黄酮（120 mg/kg），收集粪便及不同时间点的血浆样品。采用UHPLC-Q-TOF-MS/MS技术分析粪便中原型成分及代谢产物；以黄芩苷为内标，建立UPLC-MS/MS测定大鼠血浆中斯皮诺素含量的方法，并应用于斯皮诺素在正常与抗生素大鼠体内药动学比较研究。结果 正常及抗生素大鼠粪便中共鉴定了24个化合物，包括9个原型成分（维采宁II、斯皮诺素、牡荆素、异牡荆素、当药黄素、异当药黄素、山柰酚-3-O-芸香糖苷、6'-p-香豆酰斯皮诺素、6'-阿魏酰斯皮诺素）和15个代谢产物。正常大鼠中主要发生氢化、糖基化等4种代谢反应，抗生素干预后发生了脱甲氧基、去羟基化等6种代谢反应。与正常组相比，抗生素组大鼠血浆中斯皮诺素的血药浓度显著降低（P＜0.05），达峰时间和半衰期显著升高（P＜0.05）。结论 抗生素干预会导致酸枣仁黄酮类成分在大鼠体内代谢反应紊乱，并影响斯皮诺素的药动学行为。

Objective To compare the differences of in vivo metabolic transformation reaction of total flavonoids in Suanzaoren (Ziziphi Spinosae Semen, ZSSF) in normal and antibiotic-treated rats and pharmacokinetic characteristic changes of spinosin in plasma of both groups. Methods Rats were treated with antibiotics by intragastric administration, normal and antibiotic-treated rats were ig ZSSF (120 mg/kg), then feces and plasma from different time periods were collected. UHPLC-Q-TOF-MS/MS was used to analyze the prototype components and metabolites in feces, and baicalin was used as internal standard to establish a UPLC-MS/MS method for the determination of spinosin in rat plasma, which was applied to the comparative study of pharmacokinetics between normal and antibiotic-treated rats. Results A total of 24 compounds were identified from both normal and antibiotic-treated rats, including nine prototype components (vitzenin II, spinosin, vitexin, isovitexin, swertisin, isoswertisin, kaempferol-3-O-rutinoside, 6'-p-couma acylspinosin, 6'-feruloyl spinosin) and 15 metabolites. In normal rats, four metabolic reactions such as hydrogenation and glycosylation were mainly occurred, and six metabolic reactions such as demethoxylation and dehydroxylation were occurred after antibiotic intervention. Compared with normal group, plasma concentration of spinosin in antibiotic-treated group was significantly decreased (P < 0.05), while peak time and half-life were significantly prolonged (P < 0.05). Conclusion Antibiotic intervention can lead to metabolic disorder of ZSSF in rats and affect the pharmacokinetic behavior of spinosin.

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山西省科技厅中央引导地方科技发展资金项目(YDZJSX2021C025);山西省自然科学基金面上项目(20210302123237,20210302123470);山西省卫生健康委"十大晋药"项目(ZYCZL 2020007);山西中医药大学青年科学家培育项目(2021PY-QN-07)