阿托伐他汀对人脐静脉内皮细胞TLR4及下游MyD88依赖性信号转导通路的影响

摘要

Objective To investigate the anti-atherosclerotic effect of atorvastatin on the expression of TLR4 and its downstream signal transduction pathway in human umbilical vein endothelial cells (HUVECs) .Methods LPS stimulated HUVECs were treated with atorvastatin for 24 h .The mRNA expression of TLR4 ,MyD88 and TRAF-6 were measured by real-time PCR .Protein level of TLR4 ,MyD88 and TRAF-6 were measured by western blotting .Results The mRNA expression of TLR4 ,MyD88 and TRAF-6 increased inducing by LPS ,and were significantly decreased after atorvastatin treatment .LPS increased protein level of TLR4, MyD88 and TRAF-6 ,which were markedly inhibited by atorvastatin .Conclusion Atorvastatin reduces the expression of TLR4 ,and influences the MyD88-dependent signaling pathway of TLR4 .These findings suggest that atorvastatin may exert the function of an-ti-artherosclerosis through blocking the MyD88-dependent signaling pathway of TLR4 .%目的 研究阿托伐他汀(ATV)对Toll样受体4(TLR4)及其下游信号转导通路主要元件下游髓样分化因子88(MyD88)及肿瘤坏死因子受体相关因子-6(TRAF-6)表达的影响,探讨ATV防治动脉粥样硬化(AS)的机制.方法 体外培养人脐静脉内皮细胞,用脂多糖(LPS)刺激并加入ATV干预24 h,收集细胞,用荧光定量PCR方法测定TLR4、MyD88及TRAF-6 mRNA表达;用Western blotting法测定TLR4、MyD88及TRAF-6蛋白表达.结果 用LPS刺激人脐静脉内皮细胞后,引起TLR4 、MyD88和TRAF-6的高表达(与空白对照组比较差异有统计学意义,P＜0.01),用ATV干预以后显著抑制TLR4 、MyD88及TRAF-6的表达(与模型组比较差异有统计学意义,P＜0.01).结论 ATV可阻断TLR4高表达,同时阻断TLR4胞内信号转导的MyD88依赖性途径,这可能是ATV抗AS的作用机制之一.