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目的探讨氧化型低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)刺激人单核细胞株THP1对Notch1表达及分泌细胞因子的影响,探讨其对动脉粥样硬化(atherosclerosis,AS)发病的可能作用机制。方法将人单核细胞株(THP1)经氟波酯(PMA)刺激转化为巨噬细胞后给予不同浓度ox-LDL刺激,相差显微镜动态观察细胞形态变化,RT-PCR检测不同浓度ox-LDL刺激后细胞表面Notch1 mRNA水平,采用Western印迹测定Notch1蛋白表达,采用ELISA法测定上清液中血管细胞黏附分子-1(vascular cell adhesive molecule-1,VCAM-1)和单核细胞趋化分子-1(monocyte chemoattractant pro-tein-1,MCP-1)浓度。结果 ox-LDL诱导48 h后巨噬细胞形态发生树突样细胞改变;与对照组相比,ox-LDL能刺激巨噬细胞表面Notch1蛋白和mRNA表达升高(P<0.05),培养上清液中VCAM-1和MCP-1表达升高(P<0.05),在50 mg/L浓度下诱导最佳。结论 ox-LDL能够刺激THP1细胞诱导Notch1表达增加,同时能增加动脉粥样硬化相关细胞因子VCAM-1和MCP-1的分泌,ox-LDL致动脉粥样硬化作用可能部分由Notch1介导。
Objective To investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the expression of Notch1 and the secretion of cytokines in human monocytic cell line THP1, and to explore its effect on the pathogenesis of atherosclerosis Possible mechanism of action. Methods Human mononuclear cell line (THP1) was stimulated with PMA and then stimulated with different concentrations of ox-LDL. The morphological changes of cells were observed under phase contrast microscope. The concentrations of ox-LDL The expression of Notch1 mRNA was detected by Western blot. The expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic molecule-1 (monocyte chemoattractant pro-tein-1, MCP-1) concentrations. Results Ox-LDL stimulated the expression of Notch1 protein and mRNA on the macrophages compared with the control group (P <0.05), and the supernatants of the culture supernatants The expression of VCAM-1 and MCP-1 in fluid was increased (P <0.05), and the best induction was at 50 mg / L. Conclusion Ox-LDL can stimulate Notch1 expression in THP1 cells and increase the secretion of atorvastatin-related cytokines VCAM-1 and MCP-1. Ox-LDL-induced atherosclerosis may be partly mediated by Notch1.