孕烷X受体介导佐米曲坦对大鼠肝细胞色素P450 CYP 3A的诱导作用  

Induction of rat hepatic cytochrome P-450 3A by zolmitriptan mediated with pregnane X receptor

作　　者：邢峰[1] 余露山[1] 曾苏[1] 

机构地区：[1]浙江大学药学院药物分析和药物代谢实验室,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2009年第3期249-254,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30600772)

摘　　要：目的:考察佐米曲坦对大鼠肝细胞色素P450 CYP3A1/2的诱导是否由孕烷X受体(PXR)介导。方法:在构建的基于PXR的荧光素酶报告基因上,观察不同浓度佐米曲坦(10、50、100μmol.L-1)对大鼠肝细胞色素P450 CYP3A1/2的诱导作用。以经典的诱导剂16α-氰基孕烯醇酮(PCN)作为阳性对照,空白溶剂(DMSO)作为阴性对照。结果:与阴性对照组相比,阳性对照组、佐米曲坦在100μmol.L-1浓度时,对CYP3A1有明显的诱导作用,活性分别增加了1.93、1.96倍(P<0.05);阳性对照组、佐米曲坦10μmol.L-1、50μmol.L-1浓度组对CYP3A2也有明显的诱导作用,其活性分别增加了2.51、2.10、1.63倍(P<0.01、<0.05)。结论:PXR通路是佐米曲坦诱导大鼠CYP3A1/2的一个重要途径。Objective： To investigate whether pregnane X receptor （PXR） is involved in the induction of rat hepatic cytochrome P450 3A1/2 by zolmitriptan. Methods： The induction effects of zolmitriptan were investigated in three concentrations （100μmol.L^-1,50 μmol.L^-1and 10 μmol.L^-1） using luciferase report gene method based on PXR. Pregnenolone-16α-carbonitrile （PCN） was used as the positive control and the solvent DMSO as the negative control. Results： Compared with the negative groups,the positive and high level zolmitriptan groups exhibited a significant induction effect on CYP 3A1, the activity increased to 1.93 and 1.96 times, respectively（P〈0.05）. The positive,middle level and low level zolmitriptan groups exhibited a significant induction effect on CYP 3A2,the activity increase to 2. 51,2. 10 and 1. 63 times, respectively（P〈0.01, 〈0.05）. Conclusions： Zolmitriptan can significantly induce CYP 3A2 inlow and middle concentrations and induce CYP 3A1 in high concentration. PXR is involved in the induction of CYP 3A1/2 by zolmitriptan.

关 键 词：细胞色素P450酶系统/遗传学 恶唑烷酮类/投药和剂量 恶唑烷酮类/分析 受体 胞质和核/代谢 肝 

分 类 号：R963[医药卫生—微生物与生化药学]