摘要
目的 阐明盐酸小檗碱及其与环孢素A合用对P4 5 0同工酶的影响。方法 采用分光光度法测定盐酸小檗碱、环孢素A及两者合用时小鼠肝微粒体红霉素N 脱甲基酶 (ERD)、氨基比林N 脱甲基酶 (ADM )的活性 ,采用RT PCR法测定CYP3A1和CYP2E1基因在给药前后的变化。结果 灌胃给药 3d和 6d ,盐酸小檗碱 (2 0 0mg·kg-1)对ERD活性没有明显的抑制作用 ,但对ADM有抑制作用 ;环孢素A(45mg·kg-1)对ERD和ADM均有抑制作用 ;盐酸小檗碱与环孢素A合用对ERD和ADM均有明显抑制作用。盐酸小檗碱与环孢素A合用对CYP3A1和CYP2E1基因均有明显抑制作用。结论 盐酸小檗碱与环孢素A合用可明显抑制药物代谢酶ERD(CYP3A1)、ADM以及CYP2E1。
OBJECTIVE: To study the effects of berberine hydrochloride(BBH) and coadministration with cyclosporine A(CsA) on liver microsomal cytochrome P450 isoenzyme in mice. METHODS: The activity of liver microsomal erythromycin N-demethylase (ERD) and aminopyrence N-demethylase(ADM) were determined by spectrophotography before and after treatment with BBH, CsA and two drug coadministration respectively. The levels of mRNA expression of CYP3A1, CYP1A1 and CYP2E1 were assayed with RT-PCR. RESULTS BBH at 200 mg·kg-1 had no significant inhibitory effect on ERD, but it exhibited the inhibitory action on ADM after oral administration of BBH for 3 or 6 days in mice. CsA at 45 mg·kg-1 markedly inhibited the activities of ERD and ADM. ERD and ADM were both inhibited by coadministration of BBH and CsA. The mRNA expression of CYP3A1 and CYP2E1 were found to be decreased markedly following exposure to the coadministration of BBH and CsA. CONCLUSION: The combination of BBH and CsA appeared to be a powerful inhibitor on ERD(CYP3A1), ADM and CYP2E1.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2002年第7期496-499,共4页
Chinese Pharmaceutical Journal
