内脂素对人单核细胞株源性巨噬细胞ATP结合盒转运蛋白A1的调控  

Expression of ATP binding cassette A1 induced by visfatin in THP-1-derived macrophages

作　　者：康静[1] 成蓓[1] 姜蕾[1] 

机构地区：[1]华中科技大学协和医院老年病科,武汉430022

出　　处：《临床心血管病杂志》2011年第9期661-664,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金(No:30471921)

摘　　要：目的:观察过氧化物酶体增殖物激活受体γ(PPARγ)信号转导通路在内脂素调控人单核细胞株(THP-1)源性巨噬细胞ATP结合盒转运蛋白A1(ABCA1)表达中的作用,探讨内脂素诱导泡沫细胞形成的机制和途径。方法:THP-1单核细胞诱导分化为巨噬细胞,随机分组,给予不同浓度和不同作用时间的内脂素进行干预,分别运用油红O染色观察细胞浆脂滴变化,反转录聚合酶链反应(RT-PCR)法和蛋白免疫印迹(Westernblot)法检测各组细胞PPARγ及ABCA1mRNA和蛋白表达,酶荧光学法检测细胞内TC和游离胆固醇(FC)含量,TC与FC之差为胆固醇酯(CE)含量。结果:与对照组比较,内脂素干预组细胞浆脂滴明显增多,细胞内FC和CE含量增加(P<0.05),PPARγ及ABCA1mRNA和蛋白表达降低(P<0.05);相关分析显示,内脂素呈浓度和时间依赖性下调PPARγ及ABCA1mRNA和蛋白的表达。结论:内脂素可能通过PPARγ信号转导通路下调ABCA1表达,减少细胞内FC流出,使细胞内CE合成增加,从而诱导泡沫细胞形成。这可能为内脂素致动脉粥样硬化发病机制的研究提供了一个新的理论依据。Objective：To investigate the role of peroxisome proliferator-activated receptor gamma（PPARγ） signal transduction pathway on the expression of ATP-binding cassette transporter A1（ABCA1） and to discuss the mechanism of THP-1-derived foam cell formation induced by visfatin. Method：THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate（PMA） for 48 h,then the macrophages were exposed to visfatin with different concentrations and time.Lipid droplets in cytoplasm were observed by Oil red O staining.The expressions of PPARγ and ABCA1 mRNA and protein were determined by reverse transcriptase polymerase chain reaction（RT-PCR） and Western blot respectively.The contents of total cholesterol（TC） and free cholesterol（FC） were detected by enzyme fluorescence analysis.The contents of cholesterol ester（CE） were calculated by the difference between TC and FC. Result：Compared with the control group,lipid droplets and the contents of FC and CE were incresed in visfatin groups（P0.05）.The expressions of PPARγ and ABCA1 mRNA and protein were down-regulated by visfatin in concentration and time-dependent manner. Conclusion：The down-regulation of ABCA1 expression was induced by visfatin via PPARγ signal transduction pathway,which induced foam cell formation.This may provide a new evidence for visfatin inducing atherosclerosis.

关 键 词：动脉粥样硬化 内脂素 过氧化物酶体增殖物激活受体γ信号通路 ATP结合盒转运蛋白A1 泡沫细胞 

分 类 号：R543.1[医药卫生—心血管疾病]