ibrolipim通过lxrα途径促进thp审审1巨噬细胞源性泡沫细胞abca1和abcg1的表达及胆固醇流出-ibraipim promotes the expression of abca1 and abc g1 in thp - 1 macrophage-derived foam cells and cholesterol efflux through lxr α pathway..docx

目录中文摘要2英文摘要4正文61 前言62 实验材料83 实验方法104 实验结果145 讨论246 结论26参考文献27附录34主要英文缩略语索引35文献综述36硕士期间发表的论文46致谢47Ibrolipim 通过 LXR α 途径促进 THP-1 巨噬细胞源性泡沫细胞 ABCA1 和 ABCG1 的表达及胆固醇流出硕士研究生：陈四国导师：唐朝克教授中文摘要目的：本研究以 THP-1 巨噬细胞源性泡沫细胞为研究对象，采用多种实验方法， 探讨 Ibrolipim 对 ABCA1（ATP-binding cassette transporter A1, ABCA1）、ABCG1（ATP-binding cassette transporter G1, ABCG1）表达和胆固醇流出的影响，并进 一步探讨其可能机制。方法: THP-1 单核细胞经 PMA 诱导贴壁后，加入 oxLDL 诱导其转化为泡沫细胞， 经各种因素处理后，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, 用实时荧光定量 PCR 和 Western 印迹分析法分别检测 ABCA1、ABCG1 和肝 X 受体 α（liver X receptor α,LXRα）mRNA 与蛋白质的水平。结果: 实验结果显示，Ibrolipim 能在基因和蛋白水平明显增加 ABCA1、ABCG1 和 LXRα 的表达，促进细胞内胆固醇流出并减少细胞内胆固醇含量。LXRα-siRNA 能减弱 Ibrolipim 上调 ABCA1 和 ABCG1 的作用，逆转 Ibrolipim 引起的细胞内 胆固醇流出增加和胆固醇含量减少。结论：Ibrolipim 通过 LXRα 途径促进 THP-1 源性巨噬细胞 ABCA1 和 ABCG1 的 表达，从而增加 THP-1 巨噬细胞源性泡沫细胞内胆固醇流出，减少细胞内胆固 醇含量。关键词：三磷酸腺苷结合盒转运体A1，三磷酸腺苷结合盒转运体G1，Ibrolipim，肝X受体，动脉粥样硬化。Ibrolipim Increases the Expression of ABCA1/G1 by LXRα Signaling Pathway in THP-1 Macrophage-Derived Foam Cells[ABSTRACT]OBJECTIVE: The objective of this study was to determine the effects and potential mechanisms of Ibrolipim on cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis.MEHTODS: In the present study, Human THP-1 cells pre-incubated oxLDL served as foam cell models. Real-time quantitative PCR and western blot were conducted to determine the effects of Ibrolipim on the expression of ABCA1 and ABCG1 and Liver X receptor α (LXRα). Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content.RESULTS: Ibrolipim significantly increased cholesterol efflux from THP-1 macrophage-derived foam cell to apoA-I or HDL. Moreover，it markedly increased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) andABCG1, In addition, LXRα was also up-regulated by Ibrolipim treatment. And LXRα small interfering RNA completely abolished the promotion effect which was