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单核细胞来源的微颗粒通过PPAR-α-SR-BI途径促进RAW264.7泡沫细胞形成的研究

Monocyte-derived microparticles promote RAW264.7 foam cell formation via the PPAR-α-SR-BI pathway

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【作者】 刘少飞匡雅姝彭盛闫建设李莹

【Author】 LIU Shao-fei;KUANG Ya-shu;PENG Sheng;YAN Jian-she;LI Ying;Dept.of Cardiology,East Hospital,Tongji University,School of Medicine;Shanghai Institute of Immunology ,Shanghai Jiaotong University;

【机构】 同济大学附属东方医院心内科上海市免疫学研究所

【摘要】 目的研究单核细胞来源微颗粒对泡沫细胞形成的影响。方法用氧化低密度脂蛋白或者低密度脂蛋白刺激RAW264.7细胞形成泡沫细胞,采用油红染色法对阳性的泡沫细胞进行染色,通过real-time PCR和Western印迹法测定微颗粒对RAW264.7细胞的受体或酶CD36、SR-A、ACAT1、nCEH、ABCA1、ABCG1、SR-BI的影响。结果单核细胞来源的微颗粒影响RAW264.7细胞的活力;单核细胞来源的微颗粒可促进RAW264.7细胞的泡沫化形成;低浓度(20μl/ml)微颗粒可轻微促进巨噬细胞对低密度脂蛋白的吞噬,但对氧化低密度脂蛋白的吞噬却没有影响;过氧化物酶体增殖物激活受体-α(PPAR-α)的激动剂可增强泡沫细胞形成,拮抗剂作用相反。单核细胞来源微颗粒可下调SR-BI在mRNA和蛋白质水平的表达。PPAR-α激动剂可下调单核细胞来源微颗粒对RAW264.7巨噬细胞中SR-BI蛋白表达,PPAR-α拮抗剂没有影响。结论单核细胞来源的微颗粒通过引起过氧化物酶体增殖物激活受体-α的表达,进而使巨噬细胞表面SR-BI的表达降低,从而促进RAW264.7泡沫细胞形成。

【Abstract】 Objective To investigate the role of the monocyte-derived microparticles( mono-MPs) in the formation of foam cells.Methods M ouse macrophage RAW264.7 cells were stimulated with oxidized lowdensity lipoprotein or lowdensity lipoprotein to form foam cells.Positive foam cells were stained with oil red staining.Real-time PCR and Western blotting were used to determine RAW264.7 Cell receptor or enzyme CD36,SR-A,ACAT1,n CEH,ABCA1,ABCG1,SR-BI.Results M ono-M Ps affected the activity of RAW264.7 cells.Mono-MPs promoted the formation of RAW264.7 foam cells; lowconcentration( 20 μl/ml) microparticles slightly promoted the phagocytosis of macrophages to low-density lipoproteins, but did not affect the intake of oxidized low-density lipoproteins.Peroxisome proliferator-activated receptor-alpha( PPAR-α) agonists enhanced foam cells formation,while the effect of PPAR-α antagonist was reversed.M ono-M Ps reduced the expression of SR-BI mRNA and protein levels.PPAR-α agonists reduced the expression of SR-BI protein in RAW264.7 macrophages,while PPAR-α antagonist had no effect.Conclusion The mono-M Ps, causing activation of the PPAR-α,induce the RAW264.7 foam cell formation via lipid uptake and the PPAR-α-SR-BI pathway.

【基金】 上海市浦东新区科委课题(PKJ2013-Y19)
  • 【文献出处】 同济大学学报(医学版) ,Journal of Tongji University(Medical Science) , 编辑部邮箱 ,2017年04期
  • 【分类号】R543.5
  • 【被引频次】3
  • 【下载频次】147
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