土忍翘薇合剂对大鼠CYP450酶活力和mRNA的调控作用  

Modulation of Tu Ren Qiao Wei decoction on activities and m RNA expressions of cytochrome P450 enzymes in rats

作　　者：黄爱芳[1] 王陈翔[1] 周晓洁 金辉[1] 周彬[1] 余旭奔 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

出　　处：《温州医科大学学报》2018年第1期57-62,共6页Journal of Wenzhou Medical University

基　　金：温州市科技计划项目(Y20140741;Y20140235);温州医科大学附属第一医院青年英才基金(qnyc010);温州医科大学附属第一医院院级孵化项目(FHY2014042)

摘　　要：目的:研究土忍翘薇合剂对大鼠细胞色素P450(CYP450)酶活力和m RNA表达的调节作用。方法:20只SD大鼠随机分为实验组和对照组,分别连续灌胃土忍翘薇合剂或纯净水14 d后,同时给予探针药非那西丁、安非他酮、氯唑沙宗和咪达唑仑,并用液相色谱-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、CYP2E1和CYP3A1酶活力变化;实时荧光定量PCR(RTPCR)用于测定CYP450的m RNA表达水平。结果:与对照组比较,实验组大鼠非西丁的清除率提高了42%,曲线下面积减少了31%,达峰浓度减少了33%(P<0.05),说明土忍翘薇合剂对CYP1A2活力具有显著诱导作用;实验组咪达唑仑的清除率提高了66%,曲线下面积和达峰浓度分别为对照组的57%和52%,表观分布容积增加了1.36倍(P<0.05),说明土忍翘薇合剂对CYP3A1活力具有显著诱导作用;安非他酮和氯唑沙宗药时曲线图和药动学参数均提示土忍翘薇合剂对CYP2B1和CYP2E1活力无明显影响。RT-PCR检测发现,实验组大鼠CYP1A2和CYP3A1 m RNA表达分别上调为对照组的2.26倍和1.94倍(P<0.05),而CYP2B1与CYP2E1 m RNA表达2组间比较差异无统计学意义(P>0.05)。结论:土忍翘薇合剂会上调CYP1A2和CYP3A1酶活力及其m RNA表达水平。Objective： To investigate the modulation of TuRenQiaoWei decoction on activities and mRNA expressions of cytochrome P450 （CYP450） enzymes in rats. Methods： Twenty SD rats were randomly divided into treatment group and control group. After treatment with TuRenQiaoWei decoction or water for 14 days, treatment group rats and control group rats were given the mixture of four probe substrates including phenacetin, bupropion, chlorzoxazone and midazolam. The plasma concentration of probes at a series of time-points were determined by liquid chromatography tandom mass spectrometry. The activities of CYP450s were evaluated 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 phenacetin and midazolam from treatment group showed significant differences compared with control group, which indicated that TuRenQiaoWei decoction induced CYP1A2 and CYP3A1 activity. And no significant difference was found in pharmacokinetic parameters of bupropion or chlorzoxazone from treatment group and control group. In addition, treatment with TuRenQiaoWei decoction significantly up-regulated the mRNA expression of CYP1A2 and CYP3A1 whereas it had no impact on CYP2B1 and CYP2E1. Conclusion： TuRenQiaoWei decoction can up-regulate the activities and mRNA expressions of CYP1A2 and CYP3A1.

关 键 词：土忍翘薇合剂  细胞色素P450酶系统  活力  RNA  信使 

分 类 号：R285.5[医药卫生—中药学]