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目的研究单核细胞株 THP-1分化为巨噬细胞、泡沫细胞过程中细胞清道夫受体 A(SRA)表达、单核细胞趋化蛋白-1(MCP-1)分泌及应用阿托伐他汀干预的情况。方法佛波醇酯诱导 THP-1细胞分化为巨噬细胞,将其分为对照组、ox-LDL 组(泡沫细胞组)、ox-LDL+阿托伐他汀组(再分为低、中、高浓度3组)。用 ELISA 法,测定细胞培养液中 MCP-1浓度。将 SRA 特异性结合配体 DiI-Ac-LDL 与细胞孵育,应用荧光显微镜观察各组细胞 SRA 蛋白表达及活性情况。并将 MCP-1浓度与 SRA 蛋白活性进行相关性分析。结果 400倍光镜下观察到细胞株 THP-1在佛波醇酯诱导下转变为泡沫细胞。与对照组相比,ox-LDL 组 MCP-1表达升高,6 h 后升高明显(P<0.05),12 h 达高峰(P<0.01),24 h 后逐渐下降(P<0.01)。阿托伐他汀药物干预,呈剂量依赖性降低 MCP-1水平。ox-LDL 组 SRA 蛋白活性水平明显高于对照组(P<0.01)。阿托伐他汀干预,呈剂量依赖性下调SRA 蛋白活性水平。各组细胞12 h MCP-1浓度与 SRA 蛋白活性水平呈明显正相关(r=0.683,P<0.01)。结论 SRA、炎症因子 MCP-1在 THP-1细胞分化为泡沫细胞过程中发挥重要作用,阿托伐他汀抑制 MCP-1与 SRA 表达,可能是其抗动脉粥样硬化形成的重要机制。
Objective To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and the expression of scavenger receptor A (SRA) during the differentiation of monocytic THP-1 cells into macrophages and foam cells. Intervention situation. Methods THP-1 cells were induced by phorbol ester into macrophages and divided into control group, ox-LDL group (foam cell group) and ox-LDL + atorvastatin group (subdivided into low, medium and high Concentration 3 groups). The concentration of MCP-1 in the cell culture medium was measured by ELISA. The SRA-specific binding ligand DiI-Ac-LDL was incubated with cells. The expression and activity of SRA protein in each group were observed by fluorescence microscopy. MCP-1 concentration and SRA protein activity were analyzed. Results The cell line THP-1 was transformed into foam cells induced by phorbol ester under 400-fold light microscope. Compared with the control group, the expression of MCP-1 in ox-LDL group increased significantly after 6 h (P <0.05), peaked at 12 h (P <0.01), and gradually decreased after 24 h (P <0.01). Atorvastatin treatment interfered with MCP-1 in a dose-dependent manner. The level of SRA protein in ox-LDL group was significantly higher than that in control group (P <0.01). Atorvastatin intervened and down-regulated the activity of SRA protein in a dose-dependent manner. The concentration of MCP-1 at 12 h was positively correlated with the activity of SRA protein (r = 0.683, P <0.01). Conclusion SRA and MCP-1 play an important role in the differentiation of THP-1 cells into foam cells. Atorvastatin inhibits the expression of MCP-1 and SRA, which may be an important mechanism of anti-atherosclerosis.