氟西汀对小鼠肝脏Ces1d,Ces1e和CYP3A11抑制作用及机制  

The effect of fluoxetin on Ces1d,Ces1e and CYP3A11 in the mouse liver

作　　者：尚伟[1] 王宇文[1] 储栋宝 熊晶[1] 刘娓[1] 刘杰[1] 陈瑞妮[1] 杨俭[1] 

机构地区：[1]南京医科大学药理学系,江苏南京210029

出　　处：《遵义医学院学报》2015年第1期15-19,共5页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81173128;NO:81373443;NO:81302855;NO:81102457);江苏省教育厅重大项目(NO:13KJA310003);高等学校博士学科点专项科研基金资助项目(NO:20123234110005)

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。Objective To study the effect of fluoxetin on drug metabolism enzymes in the mouse liver. Methods C57BL/6N mice were divided into four groups. The mice were injected intraperitoneally with equal volume of sa- line, 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 Cesle, Cesl 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 in- creases Stral3 （DEC1） expression, which down -regulates CYP3All （CYP3A4）. Conclusion The repression of the drug metabolism enzymes（ Cesl d,Cesl e,CYP3A11 ） induced by fluoxetin in the mouse liver is related to the decrease of PXR and increase of Stra13 （DEC1）.

关 键 词：氟西汀 药物代谢酶 PXR Stra13 

分 类 号：R749.8[医药卫生—神经病学与精神病学]