氧化型低密度脂蛋白对单核细胞表达尿激酶型纤溶酶原激活物受体的影响

摘要

Objective To investigate urokinase type plasminogen activator receptor(uPAR) expressions in cultured monocytes after exposure to different concentrations of oxidized low density lipoprotein(oxLDL).Methods Monocytes were isolated from healthy volunteers and purified by density gradient centrifugation and adhering assay.The monocytes were incubated with different concentrations of oxLDL (25, 50, and 100 mg/L) for 12, 24 and 48 hours.The expressions of uPAR protein and mRNA were detected with ELISA and RT-PCR respectively.Atorvastatin (5.0 μmo/L) was added to 50 mg/L oxLDL culture.After 12, 24, and 48 hours, the expressions of uPAR protein and mRNA were also detected.Results oxLDL stimulated the expressions of uPAR in monocytes in a concentration-dependent manner.The stimulating effects at moderate concentration of oxLDL (50 mg/L) were significantly inhibited by atorvastatin.Conclusion OxLDL significantly increases the expression of uPAR protein through upregulating the uPAR mRNA expression, and atorvastatin inhibits the expression of uPAR through downregulating the uPAR mRNA expression.%目的 探讨不同浓度的氧化型低密度脂蛋白(oxLDL)对体外培养单核细胞表达尿激酶型纤溶酶原激活物受体(uPAR)的影响.方法 采用密度梯度离心法及黏附法分离、提取并纯化健康人外周血单核细胞,对原代培养的单核细胞分别加入25,50,100 mg/L浓度的oxLDL,分别培养12,24,48h,测定单核细胞的uPAR蛋白表达量及uPAR mRNA的水平变化.药物干预组加入含阿托伐他汀(终浓度为5.0 μmo/L)和50 mg/L的ox-LDL的培养液培养12,24,48h,同样方法测定单核细胞的uPAR蛋白表达量及uPAR mRNA的水平变化.结果与正常组比较,oxLDL刺激组单核细胞uPAR蛋白表达水平有显著升高,并呈剂量依赖关系;oxLDL刺激组单核细胞uPAR mRNA的合成量被显著上调.阿托伐他汀干预组uPAR蛋白的表达水平及uPAR mRNA合成量的刺激效果均被显著抑制.结论 oxLDL刺激单核细胞高表达uPAR是通过转录水平的上调来刺激蛋白质合成增加的;阿托伐他汀对uPAR表达的抑制足通过下调uPAR转录水平来实现的.