【摘要】 目的探讨氟西汀对小鼠肝脏药物代谢酶(Ces1d,Ces1e和CYP3A11)的作用及机制。方法雄性C57BL/6N小鼠分为对照组(CON)、氟西汀低剂量组、氟西汀低剂量组和LPS组,分别腹腔注射等容积生理盐水、氟西汀10、20 mg/kg和LPS 2 mg/kg,连续3 d。提取肝脏组织蛋白,测定酶活性,Western Blot分析药物代谢酶(Ces1d、Ces1e、CYP3A11)、PXR和Stra13的表达。结果氟西汀明显降低小鼠肝脏总水解酶活性以及羧酸酯酶(Ces1 d,Ces1e)的表达(P<0.05、0.01);明显降低小鼠肝脏CYP3A11活性以及氧化酶(CYP3A11)的表达(P<0.05、0.01);氟西汀能浓度依赖性降低调节药物代谢酶的核受体PXR的表达(P<0.05、0.01),同时增加转录因子Stra13的表达(P<0.05、0.01)。结论氟西汀降低药物代谢酶(Ces1d、Ces1e、CYP3A11)的表达及活性可能与其降低PXR表达和增加Stra13表达有关。更多还原

【Abstract】 Objective To study the effect of fluoxetin on drug metabolism enzymes in the mouse liver.Methods C57 BL /6N mice were divided into four groups.The mice were injected intraperitoneally with equal volume of saline,10,20 mg / kg fluoxetin,or 2 mg / kg LPS,respectively for three days.The livers were perfused to remove blood and Collected for enzyme assay and Western blot analysis.Results Fluoxetin represses the expression of Ces1 e,Ces1 d and hydrolytic activity,and represses CYP3A11 and its activity in the mouse liver.Meanwhile,fluoxetin decreases PXR expression,which is an important regulator of drug metabolism enzymes,whereas increases Stra13( DEC1) expression,which down-regulates CYP3A11( CYP3A4).Conclusion The repression of the drug metabolism enzymes( Ces1 d、Ces1e、CYP3A11) induced by fluoxetin in the mouse liver is related to the decrease of PXR and increase of Stra13( DEC1).更多还原