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氟伐他汀和辛伐他汀对人脐静脉内皮细胞黏附分子-1表达的影响
Effect of fluvastatin and simvastatin on expression of VCAM-1 in human umbilical vein endothelial cells
【摘要】 目的 观察氟伐他汀和辛伐他汀对肿瘤坏死因子 (TNFα)诱导的人脐静脉内皮细胞(HUVEC)血管细胞黏附分子 1(VCAM 1)表达的影响 ,以期探讨 3 羟 3 甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂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及 1×10 -8~ 1× 10 -5mol/L浓度氟伐他汀或辛伐他汀共孵育 6h、12h和 2 4h ,采用细胞ELISA、流式细胞技术和RT PCR分别测定VCAM 1蛋白及mRNA表达水平。结果 1× 10 -7~ 1× 10 -5mol/L浓度氟伐他汀和辛伐他汀皆对TNFα诱导的VCAM 1蛋白表达及VCAM 1mRNA表达有抑制作用 ;10 -8mol/L浓度的氟伐他汀或辛伐他汀作用 12h及 6h对VCAM 1表达无影响 ,但作用 2 4h可抑制TNFα诱导的VCAM 1表达。两药对TNFα诱导HUVEC的VCAM 1表达的抑制作用呈浓度依赖性和时间依赖性。结论 氟伐他汀和辛伐他汀抑制TNFα诱导HUVEC的VCAM 1的表达 ,可能对阻止血单核细胞向血管内皮细胞聚集和黏附、延缓动脉粥样硬化的发生和发展有一定作用。
【Abstract】 Objective To observe the influence of fluvastatin and simvastatin on TNFα induced expression of vascular cell adhesion molecule 1 (VCAM 1) in human umbilical vein endothelial cells (HUVEC) 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 VCAM 1 in protein level and mRNA level was detected by endothelial cell enzyme linked immunosorbent assay(ELISA), 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 TNFα induced expression of VCAM 1 in HUVEC. The inhibition of VCAM 1 expression at 12 hour and 6 hour coincubation was only found in 1×10 -7 -1×10 -5 mol/L fluvastatin and simvastatin but not in 10 -8 mol/L. The inhibitory effect was concentration dependent and time dependent. Conclusion The inhibition of VCAM 1 expression in HUVEC and reduction of VCAM 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(CAD), independent of cholesterol lowering effect.
【Key words】 Fluvastatin; Simvastatin; Endothelium, vascular; Vascular cell adhesion molecule 1;
- 【文献出处】 中华心血管病杂志 ,Chinese Journal of Cardiology , 编辑部邮箱 ,2001年02期
- 【分类号】R543.5
- 【被引频次】32
- 【下载频次】154