抗血小板药物与阻断CD40信号对动脉粥样硬化的影响  

Effects of Antiplatelet Drugs and Inhibition of CD40 Signaling on Atherosclerosis

作　　者：张峻[1] 陈纪林[1] 顾晴[1] 关婷[1] 陈曦[1] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院冠心病诊治中心,北京市100037

出　　处：《中国循环杂志》2008年第1期57-61,共5页Chinese Circulation Journal

摘　　要：目的:探讨抗血小板药物、抗CD40L(CD40配体)抗体及合用对动脉粥样硬化的影响。方法:雄性载脂蛋白E基因敲除小鼠随机分为模型对照组(n=10)、抗血小板药物组(n=10,阿司匹林+氯吡格雷)、抗CD40L抗体组(n=8,抗CD40L抗体)、合用组(n=9,阿司匹林+氯吡格雷+抗CD40L抗体)。并取与载脂蛋白E基因敲除小鼠有相同遗传背景的健康雄性近交系C57BL/6小鼠6只作为正常对照组。测血脂、可溶性血管细胞黏附分子-1(sVCAM-1)和可溶性细胞间黏附分子-1(sICAM-1)浓度。观察主动脉组织病理形态学改变,免疫组织化学法测定斑块部位巨噬细胞、平滑肌细胞百分率。Western杂交分析测定基质金属蛋白酶-9的蛋白表达。结果:抗血小板药物及抗CD40L抗体治疗可明显降低sVCAM-1和sICAM-1浓度(P<0.01),减轻动脉粥样硬化病变,减少斑块部位巨噬细胞,增加平滑肌细胞数量(P<0.01),对血脂无影响(P>0.05),合用则作用增强(P<0.05)。抗CD40L抗体可降低基质金属蛋白酶-9的表达(P<0.01),抗血小板治疗无此作用。结论:抗血小板治疗及阻断CD40信号可抑制炎症反应,减轻动脉粥样硬化病变,稳定斑块,对血脂无影响,联合治疗有协同作用。Objective： To evaluate the effects of antiplatelet drugs, anti-CD40L antibody and their combination on atherosclerosis. Methods： Male apolipoprotein E gene knockout mice were divided into untreated control group （n=10） , antiplatelet drugs group（n=10, aspirin ＋ clopidogrel）, anti-CD40L antibody group（n=8）, and combined group（n=9, aspirin ＋ clopidogrel ＋anti-CD40L antibody）. Serum lipids, soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1 were detected. The aortas were taken for histomorphometry observation. The positive percentage of macrophage cells, smooth muscle cells were determined by immunohistochemistry, and the expression of matrix metalloproteinase-9 was mensurated by Western blotting. Results： Antiplatelet treatment and anti-CIMOL treatment could lower serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1 （ P 〈 0. 01 ）, reduced extent of atherosclerosis （ P 〈 0.05 ）. They also reduced the amount of macrophage cells, increase the amount of smooth muscle cells （ P 〈 0.05 ）. It had no impact on serum lipid （ P 〉 0. 05 ）. Combination of antiplatelet drugs and anti-CD40L antibody had better effect（ P 〈0. 05 ）. The expression of matrix metal-loproteinase-9 was decreased in anti-CD40L antibody group and combined group（P〈0.01）. Antiplatelet treatment had not this effect. Conclusion： Antiplatelet treament and anti-CD40L antibody could decrease vascular inflammation, prevent development of atherosclerosis, and make the lesions more stable. Their combination had better effect.

关 键 词：动脉粥样硬化 CD40-CD40配体 阿司匹林 氯吡格雷 载脂蛋白E基因敲除小鼠 

分 类 号：R541[医药卫生—心血管疾病]