单次给予氟西汀诱导小鼠肝脏甘油三酯积累的作用机制  

A single administration of fluoxetine induces lipid accumulation in mouse liver

作　　者：冯学敏[1] 熊晶[1] 刘娓[1] 桂海燕[1] 彭妍[1] 陈瑞妮[1] 胡刚[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：《南京医科大学学报（自然科学版）》2012年第6期733-738,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金资助(30772616;81173128;81102457);国家重点基础研究发展计划(2009CB521906)

摘　　要：目的:研究氟西汀对小鼠肝脏脂质代谢的影响。方法:小鼠腹腔注射10 mg/kg或25 mg/kg氟西汀,对照组给予生理盐水,以25 mg/kg氯氮平作为阳性对照,注射6 h或24 h后处死小鼠,取肝脏组织。用油红O染色观察肝脏中性脂肪积累;用试剂盒测定肝脏甘油三酯和总胆固醇含量;用Western blot技术测定小鼠肝脏固醇调节元件结合蛋白1c(SREBP1c)、乙酰辅酶A羧化酶(ACC1)和脂肪酸合成酶(FAS)以及羧酸酯酶1和3(CES1和CES3)的蛋白表达水平。结果:氟西汀诱导小鼠肝脏脂质积累,增加肝脏甘油三酯含量;氟西汀显著增加小鼠肝脏SREBP1c、ACC1和FAS的蛋白表达,同时小鼠肝脏CES1和CES3的蛋白表达水平显著减少。结论:氟西汀可能通过增加脂质合成基因的表达及减少脂质分解基因的表达从而诱导小鼠肝脏的脂质积累。Objective：To observe the effects of fluoxetine on the lipid metabolism in mouse liver and investigate the mechanisms. Methods：All mice received an intraperitoneal injection of saline （control）,fluoxetine （10 mg/kg or 25 mg/kg） or elozapine （25 mg/kg）. The mice were sacrificed at 6h or 24h after injection, and the livers were collected. Liver neutral lipid was determined by oil red O staining. Liver triglyeeride and total cholesterol were measured by test kits. Liver sterol regulatory element-binding protein le （SREBPlc）,aeetyl-CoA carboxylase 1 （ACC1） and fatty acid synthase （FAS） as well as carboxylesterase 1 （CES1） and earboxylesterase 3 （CES3） protein levels were determined by Western Blot. Results：Acute fluoxetine treatment induced hepatic lipid accumulation in mouse liver. Furthermore,the expression of ACC1 and FAS was evidently elevated while the expression of triaeylglycerol hydrolases, CES1 and CES3 was suppressed by fluoxetine. Meanwhile,the expression of SREBPlc,a lipid-modulating transcription factor, was also stimulated by fluoxetine. Conclusion： These data suggest that fluoxetine may upregulate lipogenesis via SREBPlc, as well as downregulate lipolysis in mouse liver, resulting in hepatic lipid accumulation.

关 键 词：氟西汀 脂质积累 甘油三酯 羧酸酯酶 肝脏 小鼠 

分 类 号：R966[医药卫生—药理学]