il审审6对thp审审1巨噬细胞源性泡沫细胞abca1和abcg1表达的影响及其机制研究-study on the effect of il - 6 on the expression of abca 1 and abc g1 in macrophage-derived foam cells of thp - 1 and its mechanism.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135 讨论216 结论23参考文献24附录30主要英文缩略语索引30文献综述32硕士期间发表的论文45致谢46IL-6 对 THP-1 巨噬细胞源性泡沫细胞 ABCA1 和ABCG1 表达的影响及其机制研究硕士研究生：肖 继导师：唐朝克教授中文摘要目的：本研究旨在探讨白介素-6（IL-6）对 THP-1 巨噬细胞源性泡沫细胞三磷酸 腺苷结合盒转运体 A1(ABCA1)和三磷酸腺苷结合盒转运体 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 单核细胞经佛波酯诱导贴壁后，加入 oxLDL 诱导其转化为泡沫细 胞，经各种因素处理后，用实时荧光定量 PCR 和 Western 印迹分别检测基因和 蛋白质的表达，运用液体闪烁计数法检测细胞内胆固醇流出，高效液相色谱法分 析细胞内总胆固醇、游离胆固醇和胆固醇酯的含量。结果: 实验结果表明，IL-6 能够明显降低 THP-1 巨噬细胞源性泡沫细胞 ABCA1 和 ABCG1 的表达，抑制细胞内胆固醇的流出。IL-6 也能够下调肝 X 受体 α（LXR α）的表达，抑制 LXR 特异性激动剂 T0901317 对 ABCA1 和 ABCG1 的表达。 相反， LXR α-siRNA 能逆转 IL-6 下调 ABCA1 和 ABCG1 的作用。同时，IL-6 呈剂量和时间依赖性诱导 JAK1/STAT3 的活化，JAK1 抑制剂 piceastannol 能够抑制 IL-6 的活化。此外，STAT3 小分子干扰 RNA 和 piceastannol 能够逆转 IL - 6对 LXR α、ABCA1 和 ABCG1 的抑制作用。结论：IL-6 能抑制 THP-1 巨噬细胞源性泡沫细胞 ABCA1 和 ABCG1 表达及胆固 醇流出。这可能是 IL-6 通过活化 JAK1-STAT3 信号途径下调 LXR α 水平，从而 降低细胞内 ABCA1 和 ABCG1 表达及细胞内胆固醇的流出。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，白细胞介 素6，肝X受体，动脉粥样硬化。Effect and Probable Mechanism of Interleukin-6 on Expression ofABCA1 andABCG1 in THP-1 Macrophage-Derived Foam Cells[ABSTRACT]OBJECTIVE: The aim of the present study was to determine the effects and potential mechanisms of IL-6 on ABCA1 and ABCG1 expression and cholesterol efflux in human macrophage foam cells.MEHTODS: In the present study, Human THP-1 cells pre-incubated oxLDL served as foam cell models. Specific mRNA was quantified by real-time PCR, protein expression by Western blotting. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content.RESULTS: IL-6 significantly decreased the expression of ABCA1 and ABCG1 and cholesterol efflux in the THP-1 macrophage-derived foam cells. Liver X receptors α (LXR α) which can regulate the expression of ABCA1 and ABCG1 were also down-regulated by IL-6 treatment. IL-6 also suppressed the effects of T0901317 towards the expression of ABCA1 and ABCG1. LXR α siRNA reversed the effect of IL-6 on ABCA1 and ABCG1. Meanwhi