他汀类药对人脐静脉内皮细胞细胞间黏附分子1表达的影响

Inhibitory effect of fluvastatin and simvastatin on expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells

目的 观察氟伐他汀 (Flu)和辛伐他汀 (Sim)对肿瘤坏死因子 (TNF)α诱导的人脐静脉内皮细胞 (HUVEC)细胞间黏附分子 (ICAM) 1表达的影响 ,探讨他汀类药物可能的非调脂抗动脉粥样硬化作用。方法 体外培养HUVEC ,加TNFα (10 0U/ml)及 1× 10 -8～ 1× 10 -5mol/L浓度Flu或Sim ,共孵育 6、12和 2 4h ,采用细胞ELISA、流式细胞技术和逆转录 聚合酶链反应测定ICAM 1蛋白及mRNA水平表达。结果 Flu和Sim皆对TNFα诱导的ICAM 1蛋白表达及ICAM 1mRNA表达有抑制作用 ,呈浓度依赖性和时间依赖性特征。结论 Flu和Sim抑制TNFα诱导的HUVECICAM 1表达 ,可能对阻止血单核细胞向血管内皮细胞募集和黏附、延缓动脉粥样硬化的发生和发展有一定作用。

Objective To observe the influence of fluvastatin and simvastatin on TNFα induced expression of intercellular adhesion molecule 1(ICAM 1) in human umbilical vein endothelial cells(HUVEC) and to investigate the non lipid mechanisms of 3 hydroxy 3 methyl glutaryl coenzyme A(HMG CoA) reductase inhibitors on anti atherosclerosis. Methods The expression of ICAM 1 in protein level and mRNA level was detected with endothelial cell enzyme linked immunosorbent assay, flow cytometric technique and RT PCR. Results Fluvastatin and simvastatin of 1×10 -8 ～1×10 -5 mol/L at 24 hour coincubation could inhibit TNF( induced expression of ICAM 1 in HUVEC. The inhibition of ICAM 1 expression was also found respectively in fluvastatin of 1×10 -7 ～1×10 -5 mol/L and simvastatin of 1×10 -8 ～1×10 -5 mol/L at 12 hour coincubation , 1×10 -6 ～1×10 -5 mol/L fluvastatin and 1×10 -7 ～1×10 -5 mol/L simvastatin at 6 hour coincubation. Their inhibitory effects were concentration dependent and time dependent. Conclusion The inhibition of ICAM 1 expression in HUVEC and reduction of ICAM 1 dependent monocytes adhesion to endothelium by fluvastatin and simvastatin may crucially contribute to the clinical benefits of HMG CoA reductase inhibitors on coronary artery disease, independent of cholesterol lowering effects.