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目的探讨抗β2糖蛋白I(β2GPI)抗体在载脂蛋白E缺陷(ApoE~(-/-))小鼠表达动脉粥样硬化相关炎症因子和血栓相关分子过程中的作用。方法将ApoE~(-/-)小鼠实施颈动脉套环手术后,随机分为生理盐水组、100μg抗β2GPI抗体组、100μg同源对照抗体(兔IgG)组以及100μgβ2GPI/抗β2GPI抗体复合物组。各组均给以高脂饮食,且每7 d腹腔注射1次相应刺激剂,6周后处死小鼠。采用HE染色观察套环侧颈动脉阻塞情况,并以免疫组织化学染色检测套环侧颈动脉TLR4、组织因子(TF)和冯·维勒布兰德因子(vWF)的表达。采用实时荧光定量PCR检测主动脉的白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的mRNA水平。结果 HE染色结果显示抗体组阻塞最为明显,免疫组织化学染色结果显示抗体组套环侧颈动脉TLR4、TF和vWF表达上调,抗体组主动脉IL-1β和TNF-α的mRNA水平明显高于其他3组。结论抗β2GPI抗体通过上调小鼠动脉血管表达炎症因子IL-1β和TNF-α,血栓相关分子TF和vWF以及TLR4的表达,促进动脉粥样斑块形成。
Objective To investigate the role of anti-β2GPI antibodies in the expression of atherosclerosis-related inflammatory cytokines and thrombus-associated molecules in apolipoprotein E deficient (ApoE ~ (- / -)) mice. Methods ApoE ~ (- / -) mice were randomly divided into saline group, 100μg anti-β2GPI antibody group, 100μg homologous control antibody (rabbit IgG) group and 100μgβ2GPI / anti-β2GPI antibody complex group. Each group were given a high-fat diet, and every 7 d intraperitoneal injection of the corresponding stimulant 1, 6 weeks after the mice were sacrificed. The occlusion of the carotid artery was observed by HE staining. The expression of TLR4, tissue factor (TF) and von Willebrand factor (vWF) were detected by immunohistochemical staining. Real-time fluorescent quantitative PCR was used to detect the mRNA levels of IL-1β and TNF-α in the aorta. Results HE staining showed the most obvious obstruction in the antibody group. Immunohistochemical staining showed that TLR4, TF and vWF were up-regulated in the carotid artery of the circumfluence side of the antibody group. The mRNA levels of IL-1β and TNF-α in the aorta of the antibody group were significantly higher than those in other groups 3 groups. Conclusion Anti-β2GPI antibody can promote the formation of atherosclerotic plaque by up-regulating the expression of inflammatory factors IL-1β and TNF-α, thrombus-associated molecules TF and vWF and TLR4 in the arteries of mice.