【摘要】 目的　观察血管紧张素Ⅱ (AngⅡ )刺激人脐静脉血管内皮细胞 (HUVEC)核因子 κB(NF κB)激活与其对肿瘤坏死因子 α(TNFα)、白介素 6 (IL 6 )表达的影响及血管紧张素 1型受体(AT1R)拮抗剂厄贝沙坦 (irbesartan ,Irb)干预后的变化 ,以探讨AngⅡ /NF κB在动脉粥样硬化 (AS)致病机制中的作用和Irb可能的抗AS效应。方法　体外培养HUVEC ,测定AngⅡ刺激下NF κB亚单位 p6 5的核易位阳性率、TNFα、IL 6的时间与浓度反应曲线 ;然后将分盘于 2 4孔板的细胞随机分为5组 (n =6 ) :正常培养对照组、AngⅡ刺激组 ,AngⅡ和 3种不同浓度的Irb共孵育组 ;采用细胞ELISA、免疫细胞化学分析分别测定TNFα、IL 6的含量和NF κBp6 5的核易位阳性率。 结果　AngⅡ(1nmol/L～ 5 μmol/L)刺激HUVEC表达TNFα、IL 6呈时间与浓度依赖性 ,其表达高峰分别为 12～2 4h、6～ 12h ,NF κBp6 5核易位阳性率亦呈时间浓度依赖性 ,高峰在 1～ 4h。厄贝沙坦 (0 0 1μmol/L、0 1μmol/L、1μmol/L)均能显著降低TNFα和IL 6表达与NF κBp6 5核易位阳性率。 结论　AngⅡ以浓度和时间依赖方式刺激HUVECNF κB激活与TNFα、IL 6表达 ,厄贝沙坦抑制HUVECNF κB激活与TNFα、IL 6表达 ,提示AngⅡ /NF κB信号途径在促进AS发病机制中起重要?更多还原

【Abstract】 Objective To observe the influence of angiotensinⅡ(AngⅡ) on nuclear factor κB(NF κB) activation as well as tumor necrosis factor α (TNFα) and interleukin 6 (IL 6) secreted by human umbilical vascular endothelial cells (HUVEC), and the effect of AngⅡ 1 type receptor(AT 1R) antagonist irbesartan(Irb) intervention on the factors above, to investigate the role of AngⅡ/NF κB in atherosclerosis (AS) and evaluate the mechanisms of AT 1R antagonist on anti atherosclerosis. Methods Cultured passage 3 5 of HUVEC in vitro were incubated with 0 2%FCS for 24 h, then stimulated by AngⅡ,estimated NF κB,TNFα,IL 6 time and concentration response curves; then chose appropriate time and concentration of AngⅡ,incubated with Irb for 2 h before AngⅡinfusion, cocultured for a suitable time. TNFα and IL 6 were measured by cell ELISA; immunocytochemical method was employed to evaluate the nuclear translocation of NF κB subunit p65.Results AngⅡ(1 nmol/L-5 μmol/L) stimulated NF κBp65 nuclear translocation and TNFα and IL 6 expression strongly in HUVEC in concentration and time dependent manner The peak expression of NF κBp65 ,TNFα and IL 6 was 1-4 h,12-24 h,6-12 h repectively. Irb (0 01 μmol/L、0 1 μmol/L、1 μmol/L) decreased NF κBp65 activation and the expression of TNFα and IL 6 significantly stimulated by AngⅡ. Conclusion AngⅡcould stimulate TNFα、IL 6 expression in HUVEC at least in part through NF κB signal transduction Irb could blockade AT 1R and inhibite NF κB activation and decrase TNFα、IL 6 expression, which suggested that AngⅡ/NF κB might play a critical role in the pathophysiology of AS by blockading AT 1R or inhibiting NF κB activation so as to decrease or inhibit the development of AS.更多还原