【摘要】 目的探讨单核细胞与血管内皮细胞相互作用对基质金属蛋白酶1(MMP-1)表达的影响及阿托伐他汀对其干预作用,为预防动脉粥样硬化提供实验依据。方法体外培养的人脐静脉内皮细胞株(HUVEC-304)及健康人外周血分离的单核细胞用于实验。用(0.6×104,1.2×105,6×105,1.2×106,6×106)单核细胞与1.2×106HUVEC-304共同培养24h;1.2×106单核细胞与1.2×106HUVEC-304共同培养(6h,12h,24h,48h);1.2×106单核细胞与1.2×106HUVEC-304共同培养加(0.01、0.05、0.10、0.50、1.00μmol/L)阿托伐他汀孵育24h后,采用细胞酶联免疫吸附试验(ELISA)法测定MMP-1表达水平。结果单核细胞不分泌MMP-1,单核细胞刺激HUVEC-304分泌MMP-1显著增加(P<0.05),单核细胞与HUVEC-3041∶1共同培养时HUVEC-304 MMP-1分泌达最高峰(P<0.001)。单核细胞与HUVEC-3041∶1共同培养,HUVEC-304 MMP-1分泌呈时间依赖性,但24h与48h MMP-1的含量差异无统计学意义(P>0.05)。0.01μmol/L阿托伐他汀对HUVEC-304表达MMP-1无影响(P>0.05),0.05、0.10、0.50、1.00μmol/L的阿托伐他汀能明显抑制HUVEC-304表达MMP-1(P<0.05),抑制效应呈浓度依赖性。结论单核细胞与血管内皮细胞相互作用使MMP-1表达上调可能加速动脉粥样硬化的进程和斑块破裂。阿托伐他汀可抑制单核细胞刺激HUVEC-304表达MMP-1。更多还原

【Abstract】 Objective To investigate the expression of matrix metalloproteinase -1(MMP-1) by interaction between monocytes and vascular endothelial cells and the intervention action of atorvastatin,which provide the experimental evidence of prevention and treatment on atherosclerosis.Methods The level of MMP-1 in 1.2×106 cultured human umbilical vein endothelial cells (HUVECs) strain(ECV-304)exposed to(0.6×104,1.2×105,6×105,1.2×106,6×106)freshly isolated normal human monocytes for 24h,or incubated with 1.2×106 monocytes for 6h,12h,24h and 48h,or incubated with (0.01,0.05,0.1,0.5,1μmol/L)atorvastatin and 1.2×106 monocytes for 24h was measured by cell enzyme linked immunosorbent assay(ELISA).Results Monocytes didn′t secrete MMP-1.The expression of MMP-1 in cocultured HUVECs remarkably increased (P<0.05) in time-dependent manner.The productions of MMP-1 in HUVECs increased up to the peak in 1:1 coculcure(P<0.001).Atorvastatin (0.05,0.1,0.5,1μmol/L)could inhibit the expression of matrix metalloproteinase -1 in HUVECs(P<0.05),but not in 0.01μmol/L.The inhibitory effect was dose-dependent.Conclusion It is suggested that enhanced MMP-1 expression induced by monocytes-endothelial cell interaction may play an important role in the pathogenesis of atherosclerosis and plaque rupture.Atorvastatin can inhibit the expression of MMP-1.更多还原