可溶性环氧化物水解酶抑制剂t-AUCB对巨噬细胞脂质代谢的影响
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国家自然科学基金(30770856);教育部新世纪优秀人才支持计划(NCET-08-0566);湖南省自然科学基金(10JJ3026);中南大学代谢与内分泌研究所基金(DY-2008-02-04)


Effects of Soluble Epoxide Hydrolase Inhibitors t-AUCB on Lipid Metabolism in Mouse Macrophage
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    摘要:

    目的观察可溶性环氧化物水解酶抑制剂t-AUCB对小鼠巨噬细胞脂质摄取及降解的影响,并探明其可能机制。 方法培养小鼠巨噬细胞RAW264.7,分别用不同浓度t-AUCB(1、10、50及100 μmol/L)干预24 h,或在100 μmol/L t-AUCB干预前1 h加入PPARγ 拮抗剂GW9662 5 μmol/L,采用 t-AUCB 0 μmol/L干预组作为空白对照。采用125Ⅰ-ox-LDL放射配基法测定小鼠巨噬细胞对氧化型低密度脂蛋白(ox-LDL)的摄取及降解,实时荧光定量PCR和Western blot分别测定小鼠巨噬细胞CD36 mRNA和蛋白表达。 结果 t-AUCB呈剂量依赖性地增加巨噬细胞125Ⅰ-ox-LDL摄取量和降解量, 0、1、10、50和100 μmol/L t-AUCB干预时,摄取量分别为414.96±46.71 μg/g、519.54±47.7 μg/g、629.04±37.97 μg/g、720.66± 48.58 μg/g和881.57±68.44 μg/g,降解量分别为16180.23±967.28 μg/g、17369.62±478.34 μg/g、21794.85±689.36 μg/g、27883.03±712.25 μg/g和30194.61±635.71 μg/g,与空白对照组比较差异显著(p<0.05),加入GW9662后100 μmol/L组摄取量降至467.80±51.98 μg/g,降解量降至16326.19±735.95 μg /g,与单独加入t-AUCB 组比较差异具有显著性(p<0.05); t-AUCB可呈剂量依赖性的增加小鼠巨噬细胞CD36 mRNA和蛋白的表达,而加入GW9662后明显抑制上述作用。 结论t-AUCB 可通过上调PPARγ-CD36信号通路分子表达增加小鼠巨噬细胞摄取和降解ox-LDL。

    Abstract:

    AimTo observe the effects of soluble epoxide hydrolase inhibitors t-AUCB on the uptake and degradation of lipid in mouse macrophage.MethodsRAW264.7 mouse macrophage was cultured, then t-AUCB in various concentration(1, 10, 50 and 100 μmol/L) were added for 24 hours, or incubated with peroxisome proliferators activated receptor gamma (PPARγ) antagonist GW9662 (5 μmol/L).0 μmol/L t-AUCB treated group was taken as empty control.After then, the uptake and degradation of oxidized low density lipoprotein (ox-LDL) in cells were detected by radioligand assay.The mRNA and protein expression of CD36 were determined by real-time PCR and Western blot .Resultst-AUCB could dose-dependently increase the uptake and degradation of ox-LDL in mouse macrophage.After stimulated with 0, 1, 10, 50 and 100 μmol/L t-AUCB, the uptake level of ox-LDL were 414.96±46.71 μg/g, 519.54±47.7 μg/g, 629.04±37.97 μg/g,720.66± 48.58 μg/g, 881.57±68.44 μg/g, and the degradation of ox-LDL were 16180.23±967.28 μg/g, 17369.62±478.34 μg/g, 21794.85±689.36 μg/g, 27883.03±712.25 μg/g, 30194.61±635.71 μg/g.However, after incubation of GW9662, the uptake and degradation of ox-LDL with 100 μmol/L t-AUCB

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赵婷婷,沈莉,赵旋,许丹焰,赵水平.可溶性环氧化物水解酶抑制剂t-AUCB对巨噬细胞脂质代谢的影响[J].中国动脉硬化杂志,2012,20(4):295~299.

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  • 收稿日期:2011-08-07
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