【作者】 夏宗玲； 陈荣； 王明丽；

【Author】 Zongling Xia,Rong Chen,Mingli Wang(ThirdAffiliated Hospital of Suzhou University,Department of Pharmacy,Changzhou,213000)

【机构】 苏州大学附属第三医院药剂科；

【摘要】 目的:建立雌性大鼠CYP3A酶诱导模型,用于CYP3A酶介导的药物-药物相互作用研究。方法 :标准喂养的雌性SD大鼠18只随机分为两组,一组为空白对照组(3只),一组为实验组(15只)。实验组分别用20、50、80、100、150mg/kg/d地塞米松连续灌胃3天诱导CYP3A酶,在第3天灌胃后的24h,分别取两组大鼠的肝组织制备肝微粒体,以睾酮为探针底物,测定CYP3A4酶活性。结果 :空白肝微粒体中睾酮代谢率为31.68%,地塞米松诱导组中睾酮代谢率为40.64、61.36、82.44、85.8、83.36%,经80mg/kg/d地塞米松诱导后大鼠睾酮代谢率提高达160.23%。结论 :以地塞米松80mg/kg/d的剂量诱导SD大鼠能够显著增加大鼠肝内CYP3A酶的活性,可用于研究CYP3A酶介导的药物-药物相互作用。更多还原

【Abstract】 Object:Female rat CYP3A induction model was established which wasused for studying CYP3A-mediated drug-drug interactions.Method:Female SD ratswhich were fed with standard diet were randomly divided into two groups,one groupwas the control group,another group for the experimental group.Experimental groupwere administered respectively 20,50,80,100,150 mg /kg /d dexamethasone bygavage for 3 days to induce CYP3A enzymes.In the third day after the 24h ofadministration,two groups of rat were took rat liver tissue and prepared rat liver microsomes respectively.CYP3A4 activity was determined with testosterone as theprobe substrate.Result:Testosterone metabolic rate was 31.68% in blank livermicrosomes,and were 40.64,61.36,82.44,85.8,83.36% in dexamethasone inducedgroup.Testosterone metabolic femalerate was impoved up to 160.23% after80mg/kg/d dexamethasone induced female rat.Conclusion:The dose ofdexamethasone 80mg/kg/d induced SD female rats could significant increase CYP3Aenzyme activity in the female rat liver,and the model could be used to study CYP3A-mediated drug-drug interactions.更多还原