依折麦布通过 LXRα 信号通路增加 THP-1 巨噬细胞源性泡沫细胞的 ABCA1/G1 表达。
Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.
机构信息
Institute of Cardiovascular Research, Life Science Research Center, University of South China, Hengyang, China.
出版信息
Acta Pharmacol Sin. 2010 Oct;31(10):1343-9. doi: 10.1038/aps.2010.166. Epub 2010 Sep 27.
AIM
To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis.
METHODS
Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays.
RESULTS
Ibrolipim 5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim.
CONCLUSION
Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.
目的
确定伊布利匹特对人巨噬细胞泡沫细胞中 ATP 结合膜盒转运体 A-1（ABCA1）和 ATP 结合膜盒转运体 G-1（ABCG1）表达的影响及其潜在机制，这可能在动脉粥样硬化形成中起关键作用。
方法
用 ox-LDL 预孵育的人 THP-1 细胞作为泡沫细胞模型。采用实时 RT-PCR 定量检测特定 mRNA，采用 Western blot 检测蛋白表达。采用胆固醇外排实验和高效液相色谱法研究细胞胆固醇处理。
结果
伊布利匹特 5 和 50μmol/L 显著增加了来自 THP-1 巨噬细胞源性泡沫细胞的胆固醇向载脂蛋白 A-I 或 HDL 的外排。此外，它还上调了 ABCA1 和 ABCG1 的表达。此外，伊布利匹特处理还上调了 LXRα。此外，LXRα 小干扰 RNA 完全消除了伊布利匹特诱导的促进作用。
结论
伊布利匹特增加了 ABCA1 和 ABCG1 的表达，并促进了胆固醇外排，这是由 LXRα 信号通路介导的。
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