豆腐果苷对人孕烷X 受体介导的CYP3A4 和MDR1 的转录调节作用

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (12): 1416-1421.

豆腐果苷对人孕烷X 受体介导的CYP3A4 和MDR1 的转录调节作用

谢海棠^1,2, 王果¹, 范岚¹, 张利生³, 戴晓畅³, 周宏灏¹

¹中南大学临床药理研究所, 长沙 410078, 湖南;
²皖南医学院弋矶山医院安徽省药物临床评价中心, 芜湖 241001, 安徽;
³昆明贝克诺顿制药有限公司, 昆明 650100, 云南

收稿日期:2008-12-31 修回日期:2009-01-05 发布日期:2020-10-30
通讯作者: 周宏灏,男,教授,中国工程院院士,研究方向:遗传药理学。范岚,女,讲师,研究方向:中药遗传药理学。
作者简介:谢海棠,女,副研究员,硕士生导师,研究方向:中药及临床定理药理学。Tel:0553-5738350 E-mail:xiehaitang@sina.com
基金资助:
中国博士后基金一等资助项目(20070410314)

Transcriptional regulation of CYP3A4 and MDR1 mediated via nuclear receptor PXR by helicid

XIE Hai-tang^1,2, WANG Guo¹, FAN Lan¹, ZHANG Li-sheng³, DAI Xiao-chang³, ZHOU Honghao¹

¹Institute of Clinical Pharmacology, Central South University, Changsha 410078, Hunan, China;
²Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, China;
³Kunming Baker Norton Pharmaceutical Co., Ltd, Kunming 650100, Yunnan, China

Received:2008-12-31 Revised:2009-01-05 Published:2020-10-30

摘要/Abstract

摘要： 目的建立和验证人孕烷X 受体(humanpregnant X receptor, hPXR) 介导的CYP3A4 、MDR1药物诱导剂的体外筛选体系, 考察豆腐果苷对hPXR 介导的CYP3A4 、MDR1 的转录调节作用。方法利用构建的双荧光素酶报告基因系统, 将表达载体和报告载体共转染HepG2 细胞, 以10 μmol/L 利福平为阳性对照, 用不同浓度(0.004 、0.04 、0.4 μmol/L) 豆腐果苷处理48 h 后裂解细胞进行双荧光素酶活性检测。结果不同浓度的豆腐果苷均不能通过激活hPXR 来介导CYP3A4 和MDR1 表达上调, 各浓度处理组的双荧光素酶比活性值与DMSO 溶媒组差异无统计学意义(P >0.05)。结论成功构建了hPXR 介导的CYP3A4 和MDR1 药物诱导剂的体外筛选体系, 并发现豆腐果苷不能通过激活hPXR 介导CYP3A4和MDR1 的表达上调。

关键词: 豆腐果苷, 人孕烷X 受体, CYP3A4, MDR1

Abstract: AIM: To establish nuclear receptor PXR-expressed CYP3A4 and MDR1 dual luciferase reporter gene platform, and analyze the effect of helicid on hPXR-mediated transcriptional regulation of CYP3A4 and MDR1 genes.METHODS: PXR expression plasmid and reporter gene plasmid of either CYP3A4 or MDR1 were constructed based upon the dual luciferase reporter gene platform, and co-transfected to HepG2 cells.The transfected cells were treated with helicid of various concentrations (0.004, 0.04 and 0.4 μmol/L) for 48 hours while rifampin (10 μmol/L) was included as the positive control.Cells were lysized and luciferase activity was determined using a Dual-luciferase reporter assay kit (Promega, Madison, WI).RESULTS: Helicid, at tested concentrations, did not significantly increase promoter activities of CYP3A4 and MDR1 in HepG2 cells transfected with PXR expression plasmid (P >0.05).CONCLUSION: Nuclear receptor PXR-expressed CYP3A4 and MDR1 dual luciferase reporter gene platforms were successfully established, and helicid does not significantly induce the transcription of CYP3A4 and MDR1.

Key words: helicid, human pregnant X receptor, CYP3A4, MDR1

中图分类号:

谢海棠, 王果, 范岚, 张利生, 戴晓畅, 周宏灏. 豆腐果苷对人孕烷X 受体介导的CYP3A4 和MDR1 的转录调节作用[J]. 中国临床药理学与治疗学, 2008, 13(12): 1416-1421.

XIE Hai-tang, WANG Guo, FAN Lan, ZHANG Li-sheng, DAI Xiao-chang, ZHOU Honghao. Transcriptional regulation of CYP3A4 and MDR1 mediated via nuclear receptor PXR by helicid[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(12): 1416-1421.

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