Zhu Xiaojie, Zhou Hong, Wang Xiaoyan, Cai Qianqian, He Chao, Xia Longfei, Zhang Guiting, Ouyang Hang
School of Medicine, Jiangsu University, Zhenjiang 212013, China.
School of Medicine, Jiangsu University, Zhenjiang 212013, China. *Corresponding author, E-mail:
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Mar;33(3):295-299.
Objective To investigate the roles of anti-beta 2 glycoprotein I antibodies (anti-β2GPI Ab) in the expressions of atherosclerosis(AS)-related inflammatory factors and pro-thrombosis molecules in apolipoprotein E-deficient (ApoE) mice. Methods ApoE mice were randomly divided into normal saline (NS) group, 100 μg anti-β2GPI Ab group, 100 μg homologous antibody (rabbit-IgG) group and 100 μg β2GPI/anti-β2GPI Ab complex group after silastic collars were placed around their carotid arteries by surgery. All mice were fed a high fat diet and corresponding stimuli were given through intraperitoneal injection at 7-day intervals. Six weeks later, the mice were executed. The blockage of carotid arteries of the operated side was observed by HE staining. The expressions of TLR4, tissue factor (TF) and von Willebrand factor (vWF) were detected by immunohistochemistry. The mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in aorta were tested by real-time quantitative PCR. Results HE staining showed that the blockage of carotid arteries in antibody group was the most obvious. The immunohistochemistry showed that the expressions of TLR4, TF and vWF in anti-β2GPI Ab group increased remarkably. Furthermore, the mRNA levels of IL-1β and TNF-α in anti-β2GPI Ab group were higher than those in the other groups. Conclusion The anti-β2GPI antibody promotes the formation of atherosclerotic plaques in mice by up-regulating the release of inflammatory cytokines IL-1β, TNF-α and thrombosis-related molecules TF, vWF and TLR4, ultimately enhancing the development of AS.
目的 探讨抗β2糖蛋白I抗体（抗-β2GPI Ab）在载脂蛋白E缺陷（ApoE）小鼠中对动脉粥样硬化（AS）相关炎症因子和促血栓形成分子表达的作用。方法 通过手术在ApoE小鼠颈动脉周围放置硅橡胶环后，将其随机分为生理盐水（NS）组、100 μg抗-β2GPI Ab组、100 μg同源抗体（兔IgG）组和100 μg β2GPI/抗-β2GPI Ab复合物组。所有小鼠均给予高脂饮食，并每隔7天通过腹腔注射给予相应刺激。6周后处死小鼠。通过苏木精-伊红（HE）染色观察手术侧颈动脉的阻塞情况。采用免疫组织化学法检测Toll样受体4（TLR4）、组织因子（TF）和血管性血友病因子（vWF）的表达。采用实时定量聚合酶链反应检测主动脉中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的mRNA水平。结果 HE染色显示抗体组颈动脉阻塞最明显。免疫组织化学显示抗-β2GPI Ab组中TLR4、TF和vWF的表达显著增加。此外，抗-β2GPI Ab组中IL-1β和TNF-α的mRNA水平高于其他组。结论 抗-β2GPI抗体通过上调炎症细胞因子IL-1β、TNF-α以及血栓形成相关分子TF、vWF和TLR4的释放，促进小鼠动脉粥样硬化斑块的形成，最终加速AS的发展。
