目的 研究人参皂苷Rg₃及其脱糖基代谢物人参皂苷Rh₂在林可霉素诱导的肠道菌群失调大鼠体内的药动学特征。方法 建立同时测定大鼠血浆中人参皂苷Rg₃及人参皂苷Rh₂的LC-MS/MS分析方法，并进行专属性、线性、回收率、准确度、精密度的考察。采用ig林可霉素诱导菌群失调大鼠模型，测定正常大鼠及模型大鼠粪便含水量及β-葡萄糖苷酶活性。正常大鼠及肠道菌群失调大鼠分别ig给予人参皂苷Rg₃（20 mg/kg），于不同时间点眼眶取血测定血药浓度。结果 与对照组比较，模型组大鼠粪便含水量显著增加（P<0.01），β-葡萄糖苷酶活性显著降低（P<0.01）；大鼠血浆中人参皂苷Rg₃的C_max、AUC_0~∞值均有所升高，但不具有显著性差异；而其活性代谢物人参皂苷Rh₂的C_max、AUC_0~t值与对照组相比显著降低（P<0.01）。结论 肠道菌群失调对人参皂苷Rg₃的药动学行为影响较小，但显著改变了其活性代谢物人参皂苷Rh₂的药动学，可能与菌群失调后导致大鼠肠道菌大幅下降进而影响了人参皂苷Rg₃的肠道脱糖代谢有关。

Objective The aim of this study was to explore the pharmacokinetics of ginsenoside Rg₃ and its deglycosylated metabolite,ginsenoside Rh₂ in lincomycin-induced gut microbiota dysbiosis rats after ig administration of ginsenoside Rg₃.Methods An LC-MS/MS analytical method was developed and validated to detect ginsenoside Rg₃ and Rh₂ in plasma of rats.The method was validated by specificity,linearity,lower limits of quantification (LLOQ),precision,accuracy,matrix effect,recovery,and stability.Lincomycin (orally,5 000 mg/kg,7 d) was selected to induce gut microbiota dysbiosis.The fecal moisture contents and the β-D-glucosidase activity were also assessed in this study.And the plasma samples were collected and analyzed after ig administration of ginsenoside Rg₃(20 mg/kg).Results The results indicated that this method could be used for the determination of the concentration of ginsenoside Rg₃ and Rh₂ in plasma of rats.The fecal moisture content in rats treated with lincomycin was significantly increased (P<0.01) and the β-D-glucosidase activity was decreased (P<0.01) compared with the control rats.The AUC_0~∞ and C_max in gut microbiota dysbiosis rats were increased,while the AUC_0~t and C_max of its active metabolite,ginsenoside Rh₂ were significantly decreased (P<0.01) compared with normal rats.Conclusion The pharmacokinetic profile of ginsenoside Rg₃ and Rh₂ is changed in gut microbiota dysbiosis rats,which partly relates to the decreased β-D-glucosidase activity.

国家自然科学基金资助项目（81202983）；江苏高校优势学科建设工程资助项目；江苏高校品牌专业建设工程资助项目（PPZY2015A070）