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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只分为5组)。实验组分别用20、50、80、100、150 mg·kg-1·d-1地塞米松连续灌胃3 d诱导CYP3A酶,灌胃3 d后的24 h,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80 mg·kg-1·d-1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80 mg·kg-1·d-1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。
OBJECTIVE: To establish a CYP3A enzyme-induced model in female rats for the CYP3A enzyme-mediated drug-drug interaction study. Methods Eighteen female SD rats were randomly divided into two groups. One group was blank control group (3 rats) and the other was experimental group (15 rats were divided into 5 groups). In the experimental group, CYP3A was induced by dexamethasone 20, 80, 80, 100, 150 mg · kg-1 · d-1 for 3 days after gavage, and 24 h after gavage for 3 days. Liver microsomes were prepared and CYP3A4 activity was measured using testosterone as probe substrate. Results The metabolic rate of testosterone in the blank liver microsomes was 31.68%. The testosterone metabolic rate in the dexamethasone group was 40.64%, 61.36%, 82.44%, 85.8% and 83.36%, respectively. After 80 mg · kg-1 · d-1 The metabolic rate of testosterone in rats induced by dexamethasone was up to 160.23%. Conclusion SD rats induced by dexamethasone 80 mg · kg-1 · d-1 can significantly increase CYP3A enzyme activity in rat liver and can be used to study the CYP3A enzyme-mediated drug-drug interaction.