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山东大学学报(医学版) ›› 2008, Vol. 46 ›› Issue (12): 1136-1140.

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血凝素样氧化低密度脂蛋白受体1对THP-1单核巨噬细胞源泡沫细胞MMP-9表达的影响及辛伐他汀的干预作用

王梦 吕以杰   

  1. 1.山东大学医学院,济南 250012; 2. 山东大学附属济南市中心医院心血管内科, 济南 250013
  • 收稿日期:2007-12-12 出版日期:2008-12-16 发布日期:2009-12-16
  • 通讯作者: 吕以杰(1957- ),男,教授,硕士研究生导师,主要从事急性冠状动脉综合征不稳定斑块机制和血脂研究。 E-mail:lvyijie007@hotmail.com
  • 基金资助:

    济南市科技局立项课题(99622)。

Effects of Lectin-like Oxidized Low Density Lipoprotein Receptor-1 (LOX-1) on MMP-9 expression in cultured THP-1 monocyte-derived
macrophages and the protective effect of Simvastatin

 WANG Meng, LV Yi-Jie   

  1. 1.School of Medicine, Shangdong University, Jinan 250012, China;2.Department of Cardiology, Jinan Central Hospital, Shandong University, Jinan 250013, China
  • Received:2007-12-12 Online:2008-12-16 Published:2009-12-16
  • Supported by:

    王梦(1984- ),女,硕士研究生,主要从事急性冠状动脉综合征不稳定斑块机制研究。

摘要:

目的 探讨血凝素样氧化低密度脂蛋白受体1(LOX-1)对氧化低密度脂蛋白(ox-LDL)诱导的THP-1单核/巨噬细胞源泡沫细胞(THP-1 monocytederived macrophages)基质金属蛋白酶-9(MMP-9)基因表达的影响及辛伐他汀的干预作用。 方法 利用不同浓度的ox-LDL(10、20、50、100?mg/L)诱导THP-1单核/巨噬细胞源泡沫细胞,然后分别用LOX-1受体阻断剂多聚肌苷酸( Poly I)及辛伐他汀(simvastatin)进行干预,逆转录-聚合酶链反应(RT-PCR)技术检测LOX-1、MMP-9mRNA的表达水平。 结果 THP-1单核/巨噬细胞经ox-LDL诱导后LOX-1、MMP9mRNA表达显著增加,与对照组比较差异具有统计学意义(P<0.05),并与ox-LDL在10~50?mg/L浓度范围内呈现剂量-效应关系(P<0.05)。100?mg/L oxLDL与细胞共同培养时LOX-1、MMP-9mRNA表达下降可能与高浓度oxLDL对细胞的毒性作用有关。预先用Poly I封闭细胞表面部分LOX-1,再加入50mg/L ox-LDL培养, 与未加阻断剂组比较, LOX-1、MMP9mRNA表达均减少,差异具有统计学意义(P<0.05)。100μmol/L辛伐他汀加入50mg/L oxLDL共同进行细胞培养, LOX-1、MMP-9mRNA表达与未干预组比较显著下调,差异具有统计学意义(P<0.05)。结论 ox-LDL上调THP-1单核/巨噬细胞LOX-1、MMP-9mRNA表达。LOX-1作为ox-LDL的特异性受体,可介导ox-LDL致巨噬细胞源泡沫细胞MMP-9mRNA表达增加,使动脉粥样硬化斑块中细胞外基质的降解增强,斑块趋于不稳定。辛伐他汀可以通过下调细胞LOX-1 mRNA的表达减少MMP-9 mRNA的分泌,这或许是他汀类药物发挥非调脂抗炎作用稳定斑块的机制之一。

关键词: 血凝素样氧化低密度脂蛋白受体1;  基质金属蛋白酶9; 氧化低密度脂蛋白;  辛伐他汀;巨噬细胞

Abstract:

Objective to investigate the effects of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) on expression of MMP-9  mRNA  in cultured THP-1 monocyte-derived macrophages and the protective effect of simvastatin on it.  MethodsCultured THP-1 monocyte-derived macrophages were incubated with oxLDL(10mg/L, 20mg/L, 50mg/L and 100?mg/L),  pre-incubated with polyinosinic acid and then incubated with 50mg/L ox-LDL, and co-cultured with 100μmol/L simvastatin or 50mg/Lox-LDL. Expressions of LOX-1 and MMP-9mRNA were determined by reverse transcription-polymerase chain reaction(RTPCR). ResultsExpressions of LOX1 and MMP9 mRNA were increased by oxLDL and this was in a concentration-dependent fashion in 1050mg/L(P<0.05), but were decreased by 100mg/L ox-LDL. The expressions of LOX-1 and MMP-9 were down-regulated in the THP-1 monocyte-derived macrophages by 100μmol/L simvastatin combined with 50mg/L ox-LDL(P<0.05).  Conclusionox-LDL up-regulates LOX-1 and MMP-9mRNA expressions and LOX-1 may be responsible for expression of MMP-9 in the THP-1 monocyte-derived macrophages, also it can decrease the ox-LDL mediated MMP-9 expression. Simvastatin is able to down-regulate LOX-1 expression in THP-1 monocyte-derived macrophages, corresponding with a decrease of MMP-9 mRNA expression. This in vitro inhibition of LOX-1 might be one new beneficial cardiovascular pieiotroic effect of statins for stabilization of atherosclerotic plaques.

Key words: Lectin-like oxidized low density lipoprotein receptor-1 ; Matrix metalloproteinase-9; Oxidized low density lipoprotein;Monocyte-derived macrophages;  Simvastatin

中图分类号: 

  • R363.2
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