中文摘要：

以THP-1巨噬细胞源性泡沫细胞为研究对象,观察载脂蛋白A-Ⅰ与三磷酸腺苷结合盒转运体A1（ATP binding cassette transporter A1,ABCA1）的相互作用,并探讨它们相互作用的机制,以便了解载脂蛋白A-Ⅰ和ABCA1在动脉粥样硬化发生发展中的作用.THP-1巨噬细胞源性泡沫细胞经各种因素处理后,采用油红“O”染色,观察细胞内的脂滴,运用液体闪烁计数器检测细胞内胆固醇流出,高效液相色谱分析细胞内总胆固醇、游离胆固醇和胆固醇酯含量,用逆转录-聚合酶链反应和蛋白质印迹分析法分别检测ABCA1 mRNA与ABCA1蛋白质的水平.实验结果显示,载脂蛋白A-Ⅰ和腺苷酸环化酶激动剂Forskolin（FRK）引起THP-1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯减少,而腺苷酸环化酶抑制剂SQ-22536引起THP-1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯增加.载脂蛋白A-Ⅰ引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出增加.FRK引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出呈时间和浓度依赖性增加.SQ-22536引起THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平和细胞内胆固醇流出减少.结果提示,载脂蛋白A-Ⅰ可提高THP-1巨噬细胞源性泡沫细胞ABCA1蛋白质水平,增加细胞内胆固醇流出,降低细胞内胆固醇聚积.其机制可能是通过PKA信号途经使细胞ABCA1蛋白质水平增加.

英文摘要：

ATP-binding cassette transporter A1 （ABCA1） plays a crucial role in apoA-Ⅰ binding activity and promotes cellular cholesterol efflux. In order to investigate the effect of interaction between apoA-Ⅰ and ABCA1 on atherosclerosis, and to discover the mechanism of interaction between apoA-Ⅰ and ABCA1, THP-1 cells were induced to become the macrophages by the phorbol. Then THP-1 macrophages were induced to the foam cells by ox-LDL. Treatment of THP-1 macrophage derived foam cells with apoA-Ⅰ, forskolin （FRK, an adenyl cyclase activator）, and SQ-22536 （an adenyl cyclase inhibitor） for long periods of time （24 h）. In addition, THP-1 macrophage derived foam cells were treated with increasing amounts of FRK （0, 10, 20, 40 and 80 μmol/L） and treated with FRK for increasing time（0, 6, 12 and 24 h）. Cholesterol efflux, ABCA1 mRNA and protein level were determined by FJ-2107P type liquid scintillator, reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Cellular lipid accumulation was determined by Oil Red O staining and high performance liquid chromatography analysis. The cholesterol efflux of control group, apoA-Ⅰ group, FRK group, apoA-Ⅰ ＋ FRK group and apoA-Ⅰ ＋SQ-22536 group was （8.64 ± 0.83）%, （9.8 ± 0.93）%, （10.15 ± 0.98）%, （11.72 ± 1.1）%, and （6.77 ± 0.7）%, respectively. ApoA-Ⅰ resulted in a 26.7% increase in protein expression of ABCA1, and a 14.0% increase in cholesterol efflux from THP-1 macrophage derived foam cells （P 〈 0.05）. The similar results have been observed in foam cells treated with FRK. ApoA-Ⅰ, in combination with FRK, contributed to a much larger increase in protein expression of ABCA1 （80%, P 〈 0.05） and cholesterol efflux （36%, P 〈 0.05） from THP-1 macrophage derived foam cells. In converse, treatment THP-1 macrophage derived foam cells with apoA-Ⅰ and SQ-22536 markedly down-regulated protein expression of ABCA1 （26.7%, P 〈 0.05） and decreased cholesterol efflux （22.1%, P