二甲双胍抑制ob/ob肥胖小鼠肝ApoA5表达降低血浆三酰甘油水平  

Metformin reduces plasma triglycerides in ob/ob obese mice via inhibiting the hepatic apoA5 expression

作　　者：黄贤圣[1] 李蓉[2] 陈露珠 戴文 

机构地区：[1]中南大学湘雅二医院心血管内科,长沙410011 [2]中南大学湘雅二医院口腔科,长沙410011

出　　处：《中南大学学报（医学版）》2017年第12期1389-1394,共6页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(2017JJ2351);湖南省卫生和计划生育委员会项目(B2017015)~~

摘　　要：目的:探讨肥胖相关性高三酰甘油(triglyceride,TG)血症和二甲双胍治疗效应是否与载脂蛋白A5(apolipoprotein A5,ApoA5)相关。方法:对ob/ob小鼠于常规饲料和二甲双胍干预4周,测定血浆和肝TG和ApoA5的水平。IAR20肝细胞接受二甲双胍和/或ApoA5敲除干预,测定TG含量和ApoA5表达。结果:Ob/ob小鼠血浆和肝ApoA5和TG的水平明显增高,二者血浆浓度呈明显正相关,而二甲双胍呈剂量依赖性降低二者血浆和肝水平。二甲双胍呈剂量依赖性降低IAR20肝细胞TG含量和ApoA5表达,但ApoA5敲除组可消除二甲双胍上述效应。结论:Ob/ob小鼠肝ApoA5表达上调导致血浆TG升高,而二甲双胍抑制其肝ApoA5表达、降低血浆TG。Objective： To investigate the role of apolipoprotein A5（apoA5） in the pathogenesis of obesityrelated hypertriglyceridemia and the related therapeutic effects of metformin.Methods： The ob/ob mice were treated with regular chow diet and metformin for 4 weeks, and the levels of hepatic triglyceride（TG） and apoA5 were measured. Hepatic IAR20 cells were treated with metformin and/or apoA5 siRNAs, and then cellular TG contents and apoA5 expression were determined.Results： High plasma and hepatic levels of apoA5 and TG were found in ob/ob mice. The plasma levels of apoA5 were positively correlated with plasma TG in these mice. Metformin could dosedependently decrease the plasma and hepatic levels of apoA5 and TG in ob/ob mice. Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression, these effects wereattenuated by knockdown of apoA5.Conclusion： Hepatic apoA5 is up-regulated in ob/ob mice, which contributes to the elevation of plasma TG. Metformin could inhibit hepatic apoA5 expression, leading to the reduction of the plasma level of TG.

关 键 词：载脂蛋白A5 二甲双胍 三酰甘油 肥胖 

分 类 号：R589.2[医药卫生—内分泌]