阿托伐他汀抑制巨噬细胞泡沫化

Atorvastatin Inhibits The Development of Macrophages to Foam Cells

目的探讨阿托伐他汀对人外周血单核细胞源性巨噬细胞泡沫化的影响作用,为深入探讨阿托伐他汀的抗动脉粥样硬化(AS)机理提供实验依据。方法采用密度梯度离心法和塑料吸附法从人外周血中分离单核细胞,以50 nmol/L 佛波酯(PMA)刺激48 h 使之转化为巨噬细胞。细胞分为对照组与实验组,以阿托伐他汀干预后分别测定细胞内总胆固醇(TC)、游离胆固醇(FC)与蛋白的含量,观察阿托伐他汀对细胞内 TC 与蛋白比值影响的量效关系和时效关系。结果成功建立了人单核细胞源性泡沫细胞模型。经不同浓度阿托伐他汀作用后,细胞中 TC 与蛋白比值随阿托伐他汀浓度的增加而呈剂量依赖性降低(P<0.01),细胞泡沫化程度也随着药物浓度的升高而降低,且在药物浓度一定的情况下,细胞中 TC 与蛋白比值随阿托伐他汀处理时间的延长而呈时间依赖性降低(P<0.01)。结论实验结果提示阿托伐他汀通过降低细胞内 TC 的含量,一定程度上减轻巨噬细胞的泡沫化程度,从而发挥抗 AS 的作用。

Objective To investigate effects of atorvastatin on the development from macrophages （HMDM） to foam cells. Methods Monocytes were isolated from human peripheral blood by Ficoll-Hypaque density gradient centrifugation and plastic adsorptive process. The isolated cells were stimulated by phorbol 12-myristate 13-acetate （ PMA） （50 nmol/L） for 48 h and transformed to macrophages. Macrophages were co-incubated with 80 mg/L ox- idized low density lipoprotein （ox-LDL） and atorvastatin （0-100 μmol/L）, respectively for 0, 6, 12 and 24 h. Total cholesterol （TC）, free cholesterol （FC） and protein （Pro） in cultured cells were quantitatively analyzed by high performance chromatography （ HPLC） analysis and modified Lowry protein assay. Results When macrophages were incubated with 80 mg/L ox-LDL, the ratio of TC/Pro was greater than 20, and large amount of lipid droplets were displayed indicating the formation of foam cells. Atorvastatin decreased TC/Pro ratio in foam cells in a concentration and time dependent manner （0- 100 μmol/L） （ P〈0.01 ）. Conclusion The datas suggest that atorvastatin is capable of inhibiting the formation of foam cells and decreasing of cholesterol amount in macrophages.