激活视黄醇类X受体对氧化型低密度脂蛋白诱导小鼠巨噬细胞系RAW264.7凋亡的影响
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国家自然科学基金(30670880,30600242);上海市科委基础研究重点项目(05JC14037)


Effect of Retinoid X Receptor Activation on RAW264.7 Murine Macrophage Cell Line Apoptosis Induced by Oxidized Low Density Lipoprotein
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    摘要:

    目的探讨激活视黄醇类X受体对氧化型低密度脂蛋白诱导巨噬细胞凋亡的影响及其机制。方法小鼠巨噬细胞系RAW264.7经氧化型低密度脂蛋白处理24h诱导凋亡,同时观察给予视黄醇类X受体特异性配体9-cisRA或SR11237对氧化型低密度脂蛋白诱导凋亡的干预作用,MTT法检测细胞活力,流式细胞仪PI单染法和DAPI染色检测细胞凋亡,CM-H2DCFDA荧光探针测定细胞内活性氧浓度。结果RAW264.7细胞经氧化型低密度脂蛋白(100mg/L)处理24h后细胞活力较对照组下降约60,细胞凋亡百分率较对照组升高约75,10-8mol/L和10-7mol/L9-cisRA及10-7mol/LSR11237能够显著抑制氧化型低密度脂蛋白诱导引起的细胞活力下降和凋亡(P<0.05)。给予氧化型低密度脂蛋白(100mg/L)4h后细胞内活性氧水平显著升高约17倍以上,如联合给予9-cisRA(10-7mol/L)或SR11237(10-6mol/L),平均荧光强度分别下降约52和28,较氧化型低密度脂蛋白单独处理组有显著性差异(P<0.05)。结论激活视黄醇类X受体能够抑制氧化型低密度脂蛋白诱导巨噬细胞凋亡,其机制可能与减轻细胞氧化应激损伤有关。

    Abstract:

    Aim To investigate the effect and mechanism of retinoid X receptor(RXR)activation on macrophage apoptosis induced by oxidized low density lipoprotein(ox-LDL).Methods Ox-LDL-treated RAW264.7 murine macrophage cell line was induced apoptosis after 24 h.The effect of RXR special ligands 9-cisRA and SR11237 on the apoptosis induced by ox-LDL was studied.Cell viability was assayed by MTT.The apoptotic percentage of cells was measured by flow cytometry using propidium iodide(PI) staining and DAPI staining.Cellular reactive oxygen species production was detected by CM-H2DCFDA fluorescent probe.Results The cell viability of ox-LDL-treated RAW264.7 cells were decreased by about 60% and cell apoptotic percentage was increased by about 75% compared with control respectively.9-cisRA of 10-8 mol/L and 10-7 mol/L,SR11237 of 10-6 mol/L significantly inhibited this decreased cell viability and increased cell apoptotic percentage(P<0.05),which showed dose-dependent manner.Ox-LDL-treated RAW264.7 acquired significantly increasing cellular reactive oxygen species by more than 17 folds.And it was significantly reduced by 10-7 mol/L 9-cisRA to 52% and by 10-6 mol/L SR11237 to 28% compared with control.Conclusion RXR activation can inhibit macrophage apoptosis induced by ox-LDL,which may be related to reducing oxidative stress injury.

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沈玲红,何奔,周磊,胡刘华,卜军,邵琴,王力,曾锦章,王彬尧.激活视黄醇类X受体对氧化型低密度脂蛋白诱导小鼠巨噬细胞系RAW264.7凋亡的影响[J].中国动脉硬化杂志,2008,16(11):849~852.

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  • 收稿日期:2008-07-03
  • 最后修改日期:2008-10-10
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