脂联素对泡沫细胞三磷酸腺苷结合盒转运体A1表达及细胞内胆固醇含量的影响

目的通过研究脂联素对细胞内胆固醇外流的影响以及三磷酸腺苷结合盒转运子A1的功能变化,探讨其抗动脉粥样硬化作用的可能机制。方法以THP-1来源的泡沫细胞模型为研究对象,用脂联素进行体外干预;采用逆转录聚合酶链反应、酶联免疫吸附试验和高效液相色谱等方法测定干预前后三磷酸腺苷结合盒转运子A1表达和细胞内胆固醇含量的变化。结果脂联素在体外上调泡沫细胞三磷酸腺苷结合盒转运子A1mRNA和蛋白的表达,与载脂蛋白A1联合作用还能进一步增加细胞内胆固醇的流出。脂联素单独作用促进细胞内胆固醇酯转化为游离胆固醇。结论脂联素上调泡沫细胞三磷酸腺苷结合盒转运子A1表达,并促进其介导的细胞内游离胆固醇的外流;脂联素还能促进细胞内胆固醇酯的水解。

Effects of Adiponectin on ATP Binding Cassette Transporter A1 Expression and Cholesterol Efflux in THP-1 Derived Foam Cells

Aim To further discuss the anti-atherosclerotic mechanism of adiponectin,the impact of adiponectin on cholesterol efflux mediated by ATP binding cassette transporter A1(ABCA1) in THP-1 derived foam cells was studied.Methods THP-1 derived foam cells were incubated with apolipoprotein A1(apoA1),adiponectin,and apoA1 adiponectin in vitro,respectively.RT-PCR,ELISA and HPLC were used to determine the influence of adiponectin on ABCA1 mRNA and protein expression and on intracellular cholesterol content before and after treatments.Results Adiponectin could up-regulate ABCA1 mRNA and protein expression in THP-1 derived foam cells in vitro.Adiponectin alone could enhance the transformation from cholesterol ester to free cholesterol.In combination with apoA1,it could increase the ABCA1 mediated efflux of intracellular cholesterol significantly.Conclusions Adiponectin inhibit intracellular cholesterol deposit in foam cells by enhancing the hydrolysis of intracellular cholesterol ester.It can up-regulate ABCA1 expression,and accelerate ABCA1 mediated intracellular free cholesterol efflux.