抗β2GPI抗体促进巨噬细胞摄取oxLDL加速动脉粥样硬化进展  

Anti-β2GPⅠantibody promotes uptake of oxLDL by macrophages to accelerate the progression of atherosclerosis

作　　者：崔佳[1] 仇鹏 赵培[1] 贾敏[1] CUI Jia;QIU Peng;ZHAO Pei;JIA Min(Department of Laboratory,Hebei Provincial People′s Hospital,Shijiazhuang Hebei 050051,China)

机构地区：[1]河北省人民医院检验科,河北石家庄050051

出　　处：《蚌埠医学院学报》2023年第3期306-310,共5页Journal of Bengbu Medical College

摘　　要：目的:研究抗β2糖蛋白Ⅰ(β2GPⅠ)抗体在apoE基因敲除(apoE^(-/-))小鼠巨噬细胞摄取功能及动脉粥样硬化之间的关系。方法:将雄性apoE^(-/-)小鼠随机分为抗β2GPI抗体组和模型组,每组8只,均给予高脂饲料喂养8周,其中,抗β2GPI抗体组小鼠腹腔注射抗β2GPI抗体,模型组小鼠腹腔注射同等剂量0.9%氯化钠溶液稀释的同源对照IgG抗体。8周后解剖小鼠,分离小鼠主动脉根组织,行Movat染色、免疫组织化学染色,观察主动脉根部动脉粥样硬化斑块的病理组织学特点;Western blotting检测主动脉斑块中内质网应激和巨噬细胞的标志蛋白表达;腹腔巨噬细胞体外培养,抗β2GPI抗体组和模型组分别加入氧化型低密度脂蛋白(oxLDL)+抗β2GPI抗体、oxLDL刺激24 h,观察巨噬细胞摄取oxLDL情况。结果:Movat染色显示,抗β2GPI抗体组小鼠主动脉斑块增多,斑块面积较大,胶原纤维、平滑肌纤维含量均减少,与模型组相比差异有统计学意义(P<0.05~P<0.01)。免疫组织化学染色显示,抗β2GPI抗体组小鼠主动脉根部斑块巨噬细胞面积大于模型组(P<0.05)。Western blotting结果显示,抗β2GPI抗体组小鼠中内质网应激通路标志蛋白IRE1-α、p-IRE1-α、ATF6、GRP-94及巨噬细胞CD36蛋白表达量均高于模型组(P<0.05~P<0.01)。荧光染色结果显示,抗β2GPI抗体组绿色荧光强度明显强于模型组(P<0.01)。泡沫细胞油红O染色结果显示,抗β2GPI抗体组存在泡沫细胞且数量明显多于模型组(P<0.01)。结论:抗β2GPI抗体促进apoE^(-/-)小鼠巨噬细胞摄取oxLDL,加速泡沫细胞的形成,并且通过内质网应激促进CD36在巨噬细胞中的表达,加速摄取oxLDL,进而促进动脉粥样硬化进展。Objective:To investigate the role of anti-β2-glycoproteinⅠ(β2GPⅠ)antibody in the relationship between macrophage uptake and atherosclerosis in apoE knockout(apoE^(-/-))mice.Methods:The male apoE^(-/-)mice were randomly divided into the anti-β2GPⅠantibody group and model group,with 8 mice in each group,and fed with high-fat diet for 8 weeks.The mice in the anti-β2GPⅠantibody group were intraperitoneally injected with anti-β2GPⅠantibody,and the mice in the model group were intraperitoneally injected with the same dose of homologous control IgG antibody diluted with 0.9%sodium chloride solution.After 8 weeks,the mice were dissected,and the aortic root tissues were isolated for Movat staining and immunohistochemical staining to observe the histopathological characteristics of atherosclerotic plaques in the aortic root;Western blotting was used to detect the expression of marker proteins of endoplasmic reticulum stress and macrophage in aortic plaques;the peritoneal macrophages were cultured in vitro,the anti-β2GPⅠantibody group and model group were stimulated with oxidized low-density lipoprotein(oxLDL)plus anti-β2GPⅠantibody and oxLDL for 24 hours,respectively,to observe the uptake of oxLDL by macrophages.Results:Movat staining showed that the aortic plaque increased,the plaque area was larger,and the contents of collagen fibers and smooth muscle fibers were decreased in the anti-β2GPⅠantibody group compared with the model group(P<0.05 to P<0.01).Immunohistochemical staining indicated that the area of macrophages in the aortic root plaque in the anti-β2GPⅠantibody group was larger than that in the model group(P<0.05).The results of Western blotting displayed that the expression levels of marker proteins of endoplasmic reticulum stress pathway such as IRE1-α,p-IRE1-α,ATF6,GRP-94 and macrophage CD36 protein were higher than those in the model group(P<0.05 to P<0.01).The results of fluorescence staining showed that the green fluorescence intensity in the anti-β2GPⅠantibody group was sign

关 键 词：动脉粥样硬化 抗β2糖蛋白Ⅰ抗体 巨噬细胞 

分 类 号：R541.4[医药卫生—心血管疾病]