辛伐他汀对内皮细胞株ECV-304细胞分化抗原40诱导表达的影响
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Effect of Simvastatin on Cluster of differentiation 40 Expression Induced by Tumor Necrosis Factor-α/Interferon-γin ECV-304 Cell
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    摘要:

    为研究在人脐静脉内皮细胞中,3 羟3 甲基戊二酰辅酶A还原酶抑制剂(即他汀类药物)对细胞因子诱导的细胞分化抗原4 0表达的影响,采用培养的人脐静脉内皮细胞株ECV 30 4 ,联合应用肿瘤坏死因子α和干扰素γ作为刺激剂,用不同浓度辛伐他汀干预,并用流式细胞仪和逆转录—聚合酶链反应测定细胞分化抗原4 0的表达。结果发现,联合应用肿瘤坏死因子α10 0kU L和干扰素γ15 0 0kU L ,可使ECV 30 4细胞株细胞分化抗原4 0的表达明显增加,并有一定的时效关系,单独使用肿瘤坏死因子α或干扰素γ则效果不明显;辛伐他汀可减少肿瘤坏死因子α和干扰素γ所诱导的细胞分化抗原4 0的表达,随着辛伐他汀药物浓度增加(0~10 μmol L) ,细胞分化抗原4 0表达逐渐减少,呈一定的剂量依赖性。由此提示他汀类药物治疗动脉粥样硬化的抗炎和抗免疫机制中可能有细胞分化抗原4 0系统的参与

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    Aim To investigate the effect of simvastatin on CD40 expression induced by tumor necrosis factor α (TNF α) and interferon γ (IFN γ). Methods Human umbilical vein endothelial cells (hUVECs) cell line (ECV 304) were cultured with simvastatin (0~10 μmol/L) , and stimulated with 100 kU/L TNF α and 1 500 kU/L IFN γ. We detected CD40 expression levels in hUVECs by reverse transcription polymerase chain reaction (RT PCR) and flow cytometry (FCM) analysis. Results In ECV 304, exposure to TNF α (100 kU/L) plus IFN γ (1 500 kU/L) resulted in a marked increase in CD40 expression; CD40 mRNA expression reached a maximum at 9 h, and protein at 20 h. Simvastatin attenuated the expression of CD40 exposed to TNF α (100 kU/L) plus IFN γ (1 500 kU/L) in a dose dependent manner, with a maximal effect at concentration of 10 μmol/L. On mRNA level, relative intensity quantification compared with basal were 90.9%±38.8% vs 228.0%±49.6% (p<0.05); on protein level, CD40 + cells ratio were 20.1%±1.3% vs 54.1%±6.1%(p<0.05). Conclusions Simvastatin can inhibit CD40 expression induced by TNF α/IFN γ. These results may have important implications for mechanism of anti inflammatory and immunological effect of statins.

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张敏,陈桢月,陆国平,吴春芳.辛伐他汀对内皮细胞株ECV-304细胞分化抗原40诱导表达的影响[J].中国动脉硬化杂志,2003,11(3):234~237.

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  • 收稿日期:2002-09-27
  • 最后修改日期:2002-09-27
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