脂联素经肝X受体α途径对RAW 264.7巨噬细胞ABCG1表达的影响  

Adiponectin Upregulates ABCG1 Expression Through Liver X Receptor alpha Signaling Pathway in RAW 264.7 Macrophages

作　　者：梁斌[1] 白瑞[1] 韩耀霞[2] 郭晓红[2] 肖传实[2] 边云飞[1] 

机构地区：[1]山西医科大学第二医院心内科,太原030001 [2]山西医科大学第一医院心内科,太原030001

出　　处：《生物化学与生物物理进展》2015年第9期850-857,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(81170198)~~

摘　　要：泡沫细胞形成是动脉粥样硬化发生的关键环节,胆固醇逆转运可以防止泡沫细胞形成,ATP结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)在胆固醇逆转运中起着很重要的作用,可将细胞内胆固醇转运至高密度脂蛋白(high density lipoprotein,HDL).肝X受体α(liver X receptorα,LXRα)可通过调节其靶基因ABCG1的表达来调控胆固醇逆转运.脂联素有很广泛的心血管保护作用,但对RAW 264.7巨噬细胞ABCG1表达的影响尚不清楚.为了研究脂联素对RAW 264.7巨噬细胞ABCG1表达的影响及其机制,采用实时荧光定量PCR、蛋白质印迹法检测ABCG1和LXRα的表达,使用液体闪烁计数仪检测胆固醇流出率,并利用siRNA干扰技术抑制LXRα的表达来研究LXRα在脂联素调节ABCG1中的作用.结果表明,脂联素浓度依赖性和时间依赖性地上调ABCG1和LXRα的mRNA和蛋白质的表达,促进巨噬细胞胆固醇流出.经LXRα siRNA处理后,脂联素上调ABCG1的作用消失,胆固醇流出率也相应减少.上述结果提示,脂联素经LXRα途径促进RAW 264.7巨噬细胞ABCG1表达和胆固醇流出,防止泡沫细胞形成,减轻动脉粥样硬化.It has been well known that foam cells formation is one of the hallmarks of early atherosclerosis. Reverse cholesterol transport （RCT） pathway can inhibit the foam cells formation. ATP-binding cassette transporter G1 （ABCG1） plays a crucial role in RCT and anti-atherosclerosis, which mediates the effiux of cholesterol to HDL. Liver X receptor alpha （LXRα） can stimulate cholesterol effiux through ABCG1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCG1, and explored the role of LXRoL in the regulation of ABCG1 in RAW 264.7 macrophages. The expression of ABCG1 and LXRα were examined by Real-time quantitative PCR and Western blot analyses. Cellar cholesterol effiux from THP-1 macrophage was analyzed by liquid scintillation counting assays. Our results showed that adiponectin increased ABCG1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol effiux in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRa small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCG1 expression via the LXRa pathway in RAW 264.7 macrophages.

关 键 词：脂联素 动脉粥样硬化 胆固醇逆转运 ATP结合盒转运体G1 

分 类 号：R541.4[医药卫生—心血管疾病] R589.2[医药卫生—内科学]