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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

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【作者】 张新超徐成斌高岚王申五

【Author】 ZHANG Xinchao *, XU Chengbin, GAO Lan, et al. *?Beijing Hospital, Beijing 100730, China

【机构】 北京大学第二临床学院

【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.

  • 【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
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