血管生成素1通过LXRα途径调节THP-1源性泡沫细胞ABCA1、ABCG1表达及胆固醇流出  

Angiopoietin-1 mediates ABCA1,ABCG1 expression and cholesterol efflux through LXRα pathway in THP-1 derived macrophages

作　　者：欧翔 陈凌燕 周志姣[3] 夏晓丹[2] 龚朵 赵真旺 王斯琦 张强[2] 唐朝克[2] 

机构地区：[1]长沙市第一医院内分泌科,湖南省长沙市410005 [2]南华大学心血管疾病研究所动脉硬化学湖南省重点实验室南华大学医学研究实验中心分子靶标湖南省协同创新中心,湖南省衡阳市421001 [3]中南大学湘雅三医院病理科,湖南省长沙市410013

出　　处：《中国动脉硬化杂志》2017年第11期1081-1087,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81570408);湖南省自然科学基金(2017JJ2286);长沙市科技计划项目(KQ1602028)

摘　　要：目的观察血管生成素1(Ang-1)通过LXRα调节THP-1源性泡沫细胞三磷酸腺苷结合盒转运体A1(ABCA1)、ABCG1表达和胆固醇流出。方法 160 nmol/L佛波酯诱导人THP-1单核细胞分化为巨噬细胞,50 mg/L氧化型低密度脂蛋白(ox-LDL)共孵育,使其荷脂形成泡沫细胞,常规体外培养细胞;实验分为对照组和Ang-1处理组;液体闪烁计数仪检测细胞胆固醇流出水平,高效液相色谱检测细胞内脂质成分,实时荧光定量PCR和Western blot检测ABCA1、ABCG1表达;LXRα激动剂T0901317或抑制剂GGPP分别处理THP-1源性泡沫细胞。结果Ang-1显著抑制THP-1源性泡沫细胞胆固醇流出,下调ABCA1、ABCG1表达;LXRα激活剂拮抗Ang-1对ABCA1、ABCG1表达及胆固醇流出的抑制作用。结论 Ang-1可能通过抑制LXRα表达,降低ABCA1和ABCG1表达水平,减少THP-1源性泡沫细胞内胆固醇流出。Aim To investigate whether angiopoietin-1（Ang-1） regulates ATP-binding cassette transporter A1（ABCA1）,ABCG1 expression and cholesterol efflux through liver X receptor α（LXRα） in THP-1 derived macrophages.Methods THP-1 cells were incubated with 160 nmol/L phorbol ester to transform into macrophages. Subsequently,THP-1 derived macrophages were exposed to 50 mg/L oxidized low density lipoprotein（ox-LDL） and cultured with typical approaches. The experimental groups were divided into control group and Ang-1 group. Liquid scintillation counter was used to determine the efficiency of cholesterol efflux. Lipids contents were tested with high performance liquid chromatogram（HPLC）. Real-time PCR and Western blot were used to quantify the expression of ABCA1,ABCG1. THP-1 derived macrophages were pretreated with LXRα angonists T0901317 or inhibitors GGPP,respectively. Results Ang-1 obviously reduced cholesterol efflux, and downregulated ABCA1, ABCG1 expression. LXRα angonists T0901317 interfered Ang-1-inhibited ABCA1,ABCG1 expression and cholesterol efflux. Conclusion Ang-1 decreased THP-1 derived macrophages cholesterol efflux in a LXRα dependent manner and downregulated ABCA1,ABCG1 expression.

关 键 词：血管生成素1 三磷酸腺苷结合盒转运体A1 三磷酸腺苷结合盒转运体G1 胆固醇流出 肝X受体Α 

分 类 号：R0[医药卫生]