中文摘要：

目的探讨Toll样受体4（TLR4）在抗β2糖蛋白Ⅰ（β2GPⅠ）抗体诱导小鼠动脉血管黏附分子及组织因子（TF）表达中的作用。方法腹腔注射抗β2GPⅠ抗体,分别刺激C3H/He N（TLR4正常）与C3H/He J（TLR4点突变）小鼠72 h,用免疫组织化学法观察血管内膜组织中细胞黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）及E-选择素的蛋白质表达水平,用实时荧光定量PCR和western blot方法分别检测血管组织匀浆中ICAM-1、VCAM-1、E-选择素的mRNA和蛋白质表达水平,用实时荧光定量PCR和TF活性检测试剂盒分别检测血管组织匀浆中TF mRNA表达水平及其活性。结果免疫组化结果示抗β2GPⅠ抗体刺激后的C3H/He N小鼠血管内膜中ICAM-1、VCAM-1及E-selectin蛋白均表达增强。与生理盐水对照组相比,C3H/He N小鼠和C3H/He J小鼠经抗β2GPⅠ抗体刺激后,其血管组织匀浆中ICAM-1、VCAM-1、E-选择素的mRNA和蛋白质表达水平均显著增加（P均〈0.05）;但C3H/He J小鼠的ICAM-1、VCAM-1、E-选择素的mRNA和蛋白质表达水平均明显低于C3H/He N小鼠（P均〈0.05）。经抗β2GPⅠ抗体刺激的C3H/He J小鼠血管匀浆中TF mRNA表达及生物学活性明显低于C3H/He N小鼠（P〈0.05）。结论 TLR4与抗β2GPⅠ抗体刺激上调小鼠动脉血管组织表达活性分子ICAM-1、VCAM-1、E-选择素及TF密切相关,其分子机制及其在抗磷脂综合征（APS）血栓形成中的病理机制有待深入研究。

英文摘要：

Objective To investigate the roles of Toll-like receptor 4 （TLR4） in the expressions of adhesion molecules and tissue fac- tor （TF） in mouse artery induced by anti-β2-glyeoprotein I （β22GP I ） antibody. Methods TLR4-intact C3H/HeN mice and TLR4- defective C3I-L/HeJ mice were pretreated for 72 h by intraperitoneal injection with anti-β2GP I antibody. Then, the expressions of in- tercellular cell adhesion molecule-1 （ ICAM-1 ） , vascular cell adhesion molecule-I （ VCAM-1 ） and E-seleetin proteins in arterial endo- thelium were detected by an immunohistochemistry method. The levels of ICAM-1, VCAM-1 and E-selectin mRNA and proteins in ar- tery homogenates were detected by real-time quantitative PCR （qRT-PCR） and western blot, respectively. The TF activity and mRNA level in artery homogenates were determined by a commercial TF activity detection kit and qRT-PCR, respectively. Results The ex- pressions of ICAM-1, VCAM-1 and E-selectin in arterial endothelium of C3H/HeN mice increased significantly after induction with an- ti-β2GP I antibody. Compared with nolmal saline control group, the expression levels of ICAM-1, VCAM-1 and E-seleetin mRNA and proteins in artery homogenates of C3 H/HeN and C3H/HeJ mice were significantly up-regulated by anti-β2GP I antibody （P 〈 0.05）. However, the expression levels of ICAM-1, VCAM-1 and E-selectin mRNA and proteins in C3H/HeJ mice were significantly lower than those in C3H/HeN mice （P 〈 0.05 ）. Similarly, TF mRNA and activity in artery homogenates of C3H/HeN mice induced with anti-β2GP I antibody were significantly lower than that in C3H/HeJ mice （P 〈 0.05 ）. Conclusion TLR4 contributes to the expres- sions of ICAM-1, VCAM-1, E-selectin and TF in mouse artery induced by anti-β2GP I antibody. However, its molecular mechanism and correlation with the thrombosis pathogenesis of antiphospholipid syndrome （APS） remain to be further studied.