Schulz Christian, Konrad Ildiko, Sauer Susanne, Orschiedt Lena, Koellnberger Maria, Lorenz Reinhard, Walter Ulrich, Massberg Steffen
Deutsches Herzzentrum Muenchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet, Muenchen, Germany.
Thromb Haemost. 2008 Jan;99(1):190-5. doi: 10.1160/TH07-03-0235.
Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by approximately 50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.
乙酰水杨酸（ASA）和噻吩并吡啶类药物氯吡格雷是公认的抗血小板药物，可显著降低明显动脉粥样硬化患者的继发性心血管事件。然而，它们对动脉粥样硬化病变发展的影响仍存在争议。将四周龄的载脂蛋白E缺陷小鼠随机分为四组，分别给予含胆固醇饮食，同时给予ASA（5毫克/千克）、氯吡格雷（25毫克/千克）、ASA与氯吡格雷联合用药或赋形剂，持续8至12周。通过活体显微镜检查，我们发现每日给予ASA联合氯吡格雷可使体内动脉粥样硬化斑块破裂后血小板血栓形成减少约50%。然而，单独使用ASA或氯吡格雷治疗，或联合治疗8至12周，对血小板与功能失调的内皮细胞的黏附或主动脉根部或颈动脉的动脉粥样硬化病变形成均无显著影响。总之，抗血小板治疗在减少体内动脉粥样硬化斑块破裂后的血小板黏附和随后的血栓形成方面是有效的。然而，我们的数据不支持这两种药物在载脂蛋白E缺陷小鼠动脉粥样硬化一级预防中的作用。
