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

发布时间：2018-11-29 12:06

【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、205、01、00 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(P0.05),并与ox-LDL在10~50 mg/L浓度范围内呈现剂量-效应关系(P0.05)。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50 mg/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(P0.05)。100μmol/L辛伐他汀加入50 mg/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(P0.05)。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。
[Abstract]:Objective to investigate the effect of hemagglutinin like oxidized low density lipoprotein receptor 1 (LOX-1) on matrix metal eggs of THP-1 mononuclear / macrophage derived foam cells (THP-1 monocyte-derived macrophages) induced by oxidized low density lipoprotein (ox-LDL). The effect of white enzyme-9 (MMP-9) gene expression and the intervention of simvastatin. Methods THP-1 mononuclear / macrophage derived foam cells were induced by different concentrations of ox-LDL (10 / 205 / 01 mg/L), and then treated with LOX-1 receptor blocker polyinosine (Poly I) and simvastatin (simvastatin), respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of LOX-1,MMP-9mRNA. Results the expression of LOX-1,MMP-9mRNA in THP-1 monocytes / macrophages induced by ox-LDL was significantly higher than that in the control group (P0.05). There was a dose-effect relationship between ox-LDL and ox-LDL in the range of 10 ~ 50 mg/L (P0.05). The decrease of LOX-1,MMP-9mRNA expression during the co-culture of 100 mg/L ox-LDL and cells might be related to the cytotoxicity of high concentration of ox-LDL to cells. Compared with the control group, the expression of LOX-1,MMP-9mRNA was decreased after partial LOX-1, was pretreated with Poly I and then cultured with 50 mg/L ox-LDL. The difference was statistically significant (P0.05). 100 渭 mol/L simvastatin was added to 50 mg/L ox-LDL for cell culture, LOX-1,MMP-9mRNA expression was significantly decreased compared with non-intervention group, the difference was statistically significant (P0.05). Conclusion ox-LDL up-regulates the expression of LOX-1,MMP-9mRNA in THP-1 monocytes / macrophages. As a specific ox-LDL receptor, LOX-1 can mediate the increase of MMP-9mRNA expression in macrophage derived foam cells induced by ox-LDL. The degradation of extracellular matrix in atherosclerotic plaques increased and the plaque became unstable. Simvastatin can reduce the secretion of MMP-9 mRNA by down-regulating the expression of LOX-1 mRNA, which may be one of the mechanisms of statin to play a non-lipid anti-inflammatory effect to stabilize plaque.
【作者单位】：山东大学医学院;山东大学附属济南市中心医院心血管内科;
【基金】：济南市科技局立项课题(99622)
【分类号】：R363.2

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