巨噬细胞ABCA1对Ox-LDL诱导的炎症因子的调节及其意义  

Significance of ABCA1 Effects on THP-1 Macrophage Inflammatory Cytokines Induced by Oxidized Low Density Lipoprotein

作　　者：郭志刚[1] 吴平生[1] 李建华[1] 赖文岩[1] 

机构地区：[1]南方医科大学南方医院心内科,广东广州510515

出　　处：《中山大学学报（医学科学版）》2007年第1期6-10,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金资助项目(30171028);广东省自然科学基金资助项目(010616)

摘　　要：【目的】研究在氧化低密度脂蛋白(Ox-LDL)诱导作用下,ATP结合盒转运子A1(ABCA1)对巨噬细胞中细胞间黏附分子-1(ICAM-1)、单核细胞化学趋向蛋白-1(MCP-1)mRNA和蛋白质及白介素-1β(IL-1β)蛋白质表达的影响,在细胞水平证实ABCA1对动脉粥样硬化的影响。【方法】用氟波酯(PMA)刺激THP-1细胞使之转变为巨噬细胞,Ox-LDL(30μg/mL)刺激3、6、12、24h后,以荧光定量RT-PCR和Western蛋白印迹法及酶联免疫吸附法(ELISA)检测ABCA1、ICAM-1、MCP-1及IL-1β mRNA和蛋白质表达量;用反义寡核苷酸(100nmol/L)抑制ABCA1的表达,观察Ox-LDL刺激下上述指标的改变。【结果】给予Ox-LDL刺激后,巨噬细胞ABCA1、ICAM-1、MCP-1的mRNA和蛋白及IL-1β蛋白质表达均增高;给予反义寡核苷酸转染后Ox-LDL刺激3、6h,上述指标的mRNA表达降低(P<0.01),12、24h蛋白质表达降低(P<0.01)。【结论】在巨噬细胞,ABCA1可增加Ox-LDL诱导的炎症因子表达,参与动脉粥样硬化的发生。[Objective] To evaluate the effects of ATP binding cassette transporter A1 （ABCA1） on mRNA and protein expression of intercellular adhesion molecule-1 （ICAM-1） and monocyte chemoattractant protein-1 （MCP- 1） and protein expression of interleukin-1β CIL-1β） in THP-1 macrophage induced by oxidized low density lipoprotein （Ox-LDL） in order to investigate the mechanism that ABCA1 contributes to atheroscleroganesis. [Methods] Monocytic THP-1 ceils were cultured with 100 nmol/L phorbol myristate acetate （PMA） for 72 hours to lead cells into THP-1 macrophage. Ox-LDL （30 μg/mL） was added into culture media and THP-1 macrophage cells were harvested at 3, 6, 12, and 24 hours, respectively. The mRNA and protein levels of ABCA1, ICAM-1, MCP-1 and IL-1β were investigated by real-time fluorescent quantitative RT-PCR, Western blot, and ELISA methods. After phosphorothioate oligonucleotides of ABCA1 mixture were add to culture media at final concentration of 100 nmol/L, the same experiments were repeated. [Results] The mRNA and protein amounts of ABCA1, ICAM- 1, and MCP-1 and also protein amount of IL-1β were increased after macrophage incubated with Ox-LDL. Transfected with antisense oligonucleotides of ABCA1, the expressive levels of mRNA were decreased at 3 and 6 hours （P〈 0.01）, and protein at 12 and 24 hours （P〈 0.01）. [Conclusion] ABCA1 could increase the expression of inflammatory cytokines in macrophage induced by Ox-LDL and contributed to atheroscleroganesis.

关 键 词：ATP结合盒转运子A1 氧化低密度脂蛋白 巨噬细胞 动脉粥样硬化 炎症因子 

分 类 号：R856.5[医药卫生—航空、航天与航海医学]