阿托伐他汀对脂多糖诱导的人脐静脉内皮细胞Toll样受体4及炎症因子表达的影响
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Effect of Atorvastatin on Expression of Toll Like -Receptor-4 and Inflammatory Cytokines Induced by Lipopolysaccharide in Human Umbilical Vein Endothelial Cells
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    目的研究阿托伐他汀对脂多糖诱导的人脐静脉内皮细胞Toll样受体4及血凝素样氧化型低密度脂蛋白受体1、肿瘤坏死因子α及细胞间黏附分子表达的影响,探讨阿托伐他汀对炎症性疾病的影响及防治动脉粥样硬化的机制。方法体外培养人脐静脉内皮细胞,用脂多糖刺激人脐静脉内皮细胞2 h后,加入阿托伐他汀干预24 h,收集细胞,荧光定量PCR法测定Toll样受体4、髓样分化因子88、肿瘤坏死因子受体相关因子6、血凝素样氧化型低密度脂蛋白受体1、肿瘤坏死因子α及细胞间黏附分子1 的mRNA表达;Western Blotting法测定其蛋白表达。结果用脂多糖刺激人脐静脉内皮细胞后,引起Toll样受体4、髓样分化因子88、肿瘤坏死因子受体相关因子6、血凝素样氧化型低密度脂蛋白受体1、肿瘤坏死因子α及细胞间黏附分子1的高表达(p<0.01),用阿托伐他汀干预后显著抑制Toll样受体4、髓样分化因子88、肿瘤坏死因子受体相关因子6、血凝素样氧化型低密度脂蛋白受体1、肿瘤坏死因子α及细胞间黏附分子1的表达(p<0.01)。结论阿托伐他汀可抑制Toll样受体4信号转导通路主要原件及血凝素样氧化型低密度脂蛋白受体1、肿瘤坏死因子α及细胞间黏附分子1的表达,这可能是其治疗炎症性疾病及防治动脉粥样硬化作用的机制之一。

    Abstract:

    AimTo investigate the influence of atorvastatin on the expression of toll-like receptor-4(TLR4) and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1), tumor necrosis factor-α (TNF-α), intercellular adhension molecule-1(ICAM-1) in human umbilical vein endothelial cells (HUVEC), and to study its possible anti-atherosclerotic mechanism.MethodsHUVEC was cultured in vitro and stimulated with lipopolysaccharide (LPS) for 2 h, then treated with atorvastatin for 24 h, finally the mRNA expression of TLR4, myeloid differentiation factor 88(MyD88), tumour-necrosis factor receptor-associated factor 6(TRAF-6),LOX-1,TNF-α and ICAM-1 was measured with real-time PCR, the protein expression of TLR4, MyD88, TRAF-6, LOX-1, TNF-α and ICAM-1 was analyzed using Western Blotting method.ResultsLPS enhanced the expression of TLR4,MyD88,TRAF-6,LOX-1,TNF-α and ICAM-1 (p<0.01), atorvastatin decreased the high expression of TLR4,MyD88,TRAF-6, LOX-1,TNF-α and ICAM-1(p<0.01) which were stimulated by LPS.ConclusionAtorvastatin can block the high expression of TLR4 and its downstream signal transduction pathway and the high expression of LOX-1,TNF-α and ICAM-1.Maybe it’s the mechanism of action of atorvastatin to exert the function of anti-artherosclerosis.

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姜华,姜玉姬.阿托伐他汀对脂多糖诱导的人脐静脉内皮细胞Toll样受体4及炎症因子表达的影响[J].中国动脉硬化杂志,2012,20(1):37~41.

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  • 收稿日期:2011-05-25
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