【摘要】：目的探討血凝素樣氧化低密度脂蛋白受體1(LOX-1)對(duì)氧化低密度脂蛋白(ox-LDL)誘導(dǎo)的THP-1單核/巨噬細(xì)胞源泡沫細(xì)胞(THP-1 monocyte-derived macrophages)基質(zhì)金屬蛋白酶-9(MMP-9)基因表達(dá)的影響及辛伐他汀的干預(yù)作用。方法利用不同濃度的ox-LDL(10、205、01、00 mg/L)誘導(dǎo)THP-1單核/巨噬細(xì)胞源泡沫細(xì)胞,然后分別用LOX-1受體阻斷劑多聚肌苷酸(Poly I)及辛伐他汀(simvastatin)進(jìn)行干預(yù),逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)技術(shù)檢測(cè)LOX-1、MMP-9mRNA的表達(dá)水平。結(jié)果THP-1單核/巨噬細(xì)胞經(jīng)ox-LDL誘導(dǎo)后LOX-1、MMP-9mRNA表達(dá)顯著增加,與對(duì)照組比較差異具有統(tǒng)計(jì)學(xué)意義(P0.05),并與ox-LDL在10~50 mg/L濃度范圍內(nèi)呈現(xiàn)劑量-效應(yīng)關(guān)系(P0.05)。100 mg/L ox-LDL與細(xì)胞共同培養(yǎng)時(shí)LOX-1、MMP-9mRNA表達(dá)下降可能與高濃度ox-LDL對(duì)細(xì)胞的毒性作用有關(guān)。預(yù)先用Poly I封閉細(xì)胞表面部分LOX-1,再加入50 mg/L ox-LDL培養(yǎng),與未加阻斷劑組比較,LOX-1、MMP-9mRNA表達(dá)均減少,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。100μmol/L辛伐他汀加入50 mg/L ox-LDL共同進(jìn)行細(xì)胞培養(yǎng),LOX-1、MMP-9mRNA表達(dá)與未干預(yù)組比較顯著下調(diào),差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論ox-LDL上調(diào)THP-1單核/巨噬細(xì)胞LOX-1、MMP-9mRNA表達(dá)。LOX-1作為ox-LDL的特異性受體,可介導(dǎo)ox-LDL致巨噬細(xì)胞源泡沫細(xì)胞MMP-9mRNA表達(dá)增加,使動(dòng)脈粥樣硬化斑塊中細(xì)胞外基質(zhì)的降解增強(qiáng),斑塊趨于不穩(wěn)定。辛伐他汀可以通過下調(diào)細(xì)胞LOX-1 mRNA的表達(dá)減少M(fèi)MP-9 mRNA的分泌,這或許是他汀類藥物發(fā)揮非調(diào)脂抗炎作用穩(wěn)定斑塊的機(jī)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.
【作者單位】： 山東大學(xué)醫(yī)學(xué)院;山東大學(xué)附屬濟(jì)南市中心醫(yī)院心血管內(nèi)科;
【基金】：濟(jì)南市科技局立項(xiàng)課題(99622)
【分類號(hào)】：R363.2

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