Wang X Y, Zhou H, Zhu X J, Xia L F, He C, Cai Q Q, Wang T
Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Jan 25;45(1):44-48. doi: 10.3760/cma.j.issn.0253-3758.2017.01.009.
To investigate the effects of anti-β(2) glycoprotein Ⅰ(β(2)GPⅠ) antibody on atherosclerosis in ApoE deficient mice. A total of 24 male ApoE deficient mice of specific pathogen free level(six to eight-week old)were divided into normal control group, high fat diet group, high fat diet with anti-β(2)GPⅠ group, high fat diet with homologous control antibody group (=6 each group). During the feeding period, mice were weighed every 2 weeks and were intraperitoneally injected with anti-β(2)GPⅠIgG (100 μg/per) and homologous control IgG (100 μg/per) according to grouping once a week. At the 16th week, the carotid arterial lipid deposition was observed by small animal magnetic resonance imaging, and blood samples were collected from internal vein of eyeball and the concentrations of TC, TG, HDL-C and LDL-C in plasma were measured after EDTA anticoagulant treatment. AI was calculated. The mice were then sacrificed and carotid arteries were removed, hematoxylin-eosin staining was used to observe the atherosclerotic lesions near the bifurcation of carotid artery and to calculate lesion size. (1) The body weight of mice was significantly higher in the high fat diet group compared to other 3 groups(all <0.05), which was similar among high fat diet+ anti-β(2)GPⅠantibody group, high fat diet+ homologous control IgG group and normal diet control group (>0.05). (2) After 16 weeks, plasma concentrations of TC and LDL-C in high fat diet group, high fat diet+ anti-β(2)GPⅠantibody group and high fat diet+ homologous control IgG group were significantly higher than in normal diet group (all <0.05), there was no significant difference among high fat diet groups. The level of HDL-C was significantly higher in high fat diet control group than in normal diet control group. The concentration of TG was similar among groups. However, the value of AI in high fat+ anti-β(2)GPⅠ antibody group was significantly higher than in other groups (all <0.05). (3) After 16 weeks, magnetic resonance imaging revealed that mice in high fat diet+ anti-β(2)GPⅠ antibody group had more obviously lipid deposition in the carotid arteries, it was significantly higher than that in the other groups, and the cross sections of carotid arteries stained with HE also demonstrated obviously carotid lumen stenosis and the percentage of carotid plaque area to carotid artery was (37.545±1.351)% in the high fat diet+ anti-β(2)GPⅠ antibody group, it was significantly higher than normal diet group ((1.235±0.460)%), high fat diet control group((11.635±2.751)%) and high fat diet+ homologous control IgG group ((11.815±2.623)%), all <0.01. In high fat diet+ anti-β(2)GPⅠ antibody group, the area of carotid plaque was (3.121±0.124)×10(4) μm(2,) it was also significantly higher than normal diet group ((0.094±0.015)×10(4) μm(2)), high fat diet control group ((1.309±0.147)×10(4) μm(2)) and high fat diet+ homologous control IgG group ((1.027±0.228)×10(4)μm(2)), all <0.01. Anti-β(2)GPⅠ antibody can promote atherosclerotic plaque formation in high fat diet fed ApoE deficient mice.
探讨抗β2糖蛋白Ⅰ(β2GPⅠ)抗体对载脂蛋白E(ApoE)基因缺陷小鼠动脉粥样硬化的影响。选取24只特定病原体-free级(6至8周龄)雄性ApoE基因缺陷小鼠,分为正常对照组、高脂饮食组、高脂饮食+抗β2GPⅠ组、高脂饮食+同源对照抗体组(每组6只)。饲养期间,每2周称小鼠体重,按分组每周1次腹腔注射抗β2GPⅠIgG(100μg/只)和同源对照IgG(100μg/只)。第16周,采用小动物磁共振成像观察颈动脉脂质沉积情况,从眼球内静脉取血样,经乙二胺四乙酸(EDTA)抗凝处理后检测血浆总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)浓度,计算动脉粥样硬化指数(AI)。然后处死小鼠,取颈动脉,苏木精-伊红(HE)染色观察颈动脉分叉处附近动脉粥样硬化病变并计算病变面积。(1)高脂饮食组小鼠体重显著高于其他3组(均P<0.05),高脂饮食+抗β2GPⅠ抗体组、高脂饮食+同源对照IgG组和正常饮食对照组之间体重相似(P>0.05)。(2)16周后,高脂饮食组、高脂饮食+抗β2GPⅠ抗体组和高脂饮食+同源对照IgG组血浆TC和LDL-C浓度显著高于正常饮食组(均P<0.05),高脂饮食组间无显著差异。高脂饮食对照组HDL-C水平显著高于正常饮食对照组。各组TG浓度相似。然而,高脂饮食+抗β2GPⅠ抗体组AI值显著高于其他组(均P<0.05)。(3)16周后,磁共振成像显示高脂饮食+抗β2GPⅠ抗体组小鼠颈动脉脂质沉积更明显,显著高于其他组,HE染色的颈动脉横断面也显示明显的颈动脉管腔狭窄,高脂饮食+抗β2GPⅠ抗体组颈动脉斑块面积占颈动脉面积的百分比为(37.545±1.351)%,显著高于正常饮食组((1.235±0.460)%)、高脂饮食对照组((11.635±2.751)%)和高脂饮食+同源对照IgG组((11.815±2.623)%),均P<0.01。高脂饮食+抗β2GPⅠ抗体组颈动脉斑块面积为(3.121±0.124)×10⁴μm²,也显著高于正常饮食组((0.094±0.015)×10⁴μm²)、高脂饮食对照组((1.309±0.147)×10⁴μm²)和高脂饮食+同源对照IgG组((1.027±0.228)×10⁴μm²),均P<0.01。抗β2GPⅠ抗体可促进高脂饮食喂养的ApoE基因缺陷小鼠动脉粥样硬化斑块形成。