绿茶水提物对大鼠CYP450酶活力和mRNA表达的调控作用  

Modulation of green tea extract on activities and mRNA expressions of cytochrome P450 enzymes in rats

作　　者：周子晔[1] 金辉[1] 王陈翔[1] 黄爱芳[1] 王贤亲[2] 林观样[1] 

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325015 [2]温州医科大学分析测试中心,浙江温州325035

出　　处：《温州医学院学报》2015年第7期502-506,511,共6页Journal of Wenzhou Medical College

基　　金：温州市科技计划项目(Y20110169);温州医科大学附属第一医院青年英才基金资助项目(qnyc010)

摘　　要：目的:研究绿茶水提物对大鼠细胞色素P450(CYP450)酶活力和m RNA表达的影响。方法:SD大鼠随机分组,连续灌胃绿茶水提物或水14 d后,同时给予探针药非那西丁、安非他酮、甲苯磺丁脲和咪达唑仑,采用液相色谱-质谱联用技术(液质联用)测定给药后不同时间点血药浓度,计算药动学参数进而推测CYP1A2、CYP2B1、CYP2C11和CYP3A1酶活力。此外,采用实时荧光定量PCR(real-time PCR,RT-PCR)技术测定CYP450的m RNA表达水平。结果:实验组大鼠安非他酮与甲苯磺丁脲的药动学参数与对照组相比差异有统计学意义(P<0.05),推测绿茶水提物能诱导大鼠CYP2B1酶活力和抑制CYP2C11,而非那西丁与咪达唑仑参数比较差异无统计学意义(P>0.05)。RT-PCR实验发现,绿茶水提物能显著上调大鼠CYP2B1 m RNA水平并下调CYP2C11 m RNA水平,对CYP1A2与CYP3A1没有影响。结论:持续摄取绿茶会改变CYP2B1与CYP2C11酶活力和m RNA表达水平,可能会引起药物相互作用的发生。Objective： To investigate the potential effects of green tea extract on activities and mRNA ex-pressions of cytochrome P450 （CYP450） enzymes in rats.Methods： After treatment with tea extract or water for 14 days, treatment group rats and control group rats were given the mixture of 4 probe substrates including phen-acetin, bupropion, tolbutamide and midazolam. The plasma concentrations of probes at a series of time-points were determined with liquid chromatography tandom mass spectrometry. The activities of CYP450s were evalu-ated according to the pharmacokinetic parameters of corresponding substrates. Real-time PCR was applied to assess the mRNA expression levels of CYP450s.Results： The pharmacokinetic parameters of bupropion and tol-butamide from treatment group showed signiifcant differences compared with control group, which indicated that green tea extract induced CYP2B1 activity and inhibited CYP2C11 activity. And no signiifcant difference was found in pharmacokinetic parameters of phenacetin or midazolam from treatment group and control group. In ad-dition, treatment with green tea extract signiifcantly up-regulated the mRNA expression of CYP2B1 and down-regulated the mRNA expression of CYP2C11, whereas it had no impact on CYP1A2 and CYP3A1.Conclusion：Continuous ingestion of green tea can modulate the activities and mRNA expressions of CYP2B1 and CYP2C11, which may lead to an undesired interaction.

关 键 词：绿茶水提物 CYP450 酶活力 m RNA表达 大鼠 

分 类 号：R969.2[医药卫生—药理学]