中文摘要：

目的：研究甘遂与甘草合用对甘遂中毒性成分甘遂萜酯A （ Kansuinine A, KA）和甘遂萜酯B （ Kansuinine B, KB）代谢的影响。方法将正常对照组、甘草组、甘遂与甘草合用组大鼠给予相应药物处理10 d后,制备肝微粒体。将甘遂的毒性成分KA、KB与各组肝微粒体进行体外共孵育,测定孵育后体系中KA、KB的浓度,用于评价KA、KB的代谢情况。另取正常大鼠肝微粒体,分别加入 CYP3A4、CYP2D6、CYP2C9、CYP1A2、CYP2C19的抑制剂红霉素、盐酸苯海拉明、苯溴马隆、西咪替丁和氟康唑,与KA、KB进行体外共孵育,检测孵育后体系中KA、KB的浓度,阐明参与KA、KB代谢的CYP酶亚型。取正常大鼠肝微粒体,分别加入甘草酸与甘草次酸,与KA、KB体外共孵育,测定孵育后体系中KA、KB的浓度,评价甘草酸与甘草次酸对KA、KB代谢的影响。结果甘遂与甘草合用组微粒体中KA、KB的含量明显高于正常对照组和甘遂组,表明甘遂与甘草合用使甘遂中毒性成分KA、KB的代谢受到抑制。与红霉素、盐酸苯海拉明、苯溴马隆、西咪替丁和氟康唑共孵育的微粒体中KA、KB的含量均明显高于空白对照组,表明 CYP3A4、CYP2D6、CYP2C9、CYP1A2、CYP2C19均参与了KA、KB的代谢。与甘草酸和甘草次酸共孵育,体系中KA、KB的浓度明显高于空白对照组。CYP3A4、CYP2D6、CYP2C9、CYP1A2表明甘草酸和甘草次酸能够抑制KA、KB的代谢。结论 CYP2C19均可能参与了甘遂毒性成分 KA、KB 的代谢,甘遂与甘草合用能够抑制CYP3A4、CYP2D6、CYP2C9、CYP1A2及CYP2C19的活性,而使KA、KB的代谢减慢,产生蓄积；另外,

英文摘要：

Aim To study the combined effect Euphor-bia kansui of and Glycyrrhiza uralensis on metabolism of Kansuinine A and Kansuinine B. Methods Control, GU and GU plus EK groups were treated for 10 days, respectively. Then the liver microsomes were pre-pared. KA and KB were incubated with microsomes of each group, and concentrations of KA and KB were measured to reflect the metablism of KA and KB. E-rythromycin, diphenhydramine hydrochloride,benzbro-marone, cimetidine, fluconazole the inhibitors of CYP3 A4 , CYP2 D6 , CYP2 C9 , CYP1 A2 , CYP2 C19 respectively, were incubated with KA and KB. Con-centrations of KA and KB were measured to reveal the cytochrome P450 isoforms which involved in the metab-olism of them. KA and KB were incubated with glycyr-rhizic acid and enoxolone. Then concentrations of KA and KB were measured to reveal the effects of glycyr-rhizic acid and enoxolone to KA and KB. Results Concentrations of KA and KB in GU plus EK group were significantly higher than those in control and EK groups, which showed that the metablisom of KA and KB was inhibited in GU plus EK group. In addition, concentrations of KA and KB were higher in microsomes incubated with erythromycin, diphenhydramine hydrochloride, benzbromarone, cimetidine and fluconazole than in control group, which revealed that the metablism of KA and KB was slowed down when CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19 were inhibited. They may participate in the metablisom of KA and KB. After incubation with glycyrrhizic acid and enoxolone, the metablism of KA and KB was slowed down. Conclusions KA and KB may be the substrates of CYP2C19. GU plus EK can inhibit the activity of CYP2C19, which resulted in KA and KB metablism slowing down and accumulation. In addition, glycyrrhizic acid and enoxolone can inhibit the metablism of KA and KB. It may be one of the reasons of increased toxicity of GU plus EK.