Kariyazono Hiroko, Nakamura Kazuo, Arima Junko, Ayukawa Osamu, Onimaru Shunji, Masuda Hiroshi, Iguro Yoshifumi, Majima Hideyuki J, Sakata Ryuzo, Yamada Katsushi
Department of Clinical Pharmacy and Pharmacology, Division of Maxillofacial Radiology and Department of Space Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Blood Coagul Fibrinolysis. 2004 Mar;15(2):157-67. doi: 10.1097/00001721-200403000-00007.
To compare property in anti-platelet effects of aspirin (a cyclooxygenase inhibitor), cilostazol (a phosphodiesterase III inhibitor) and ramatroban (a specific thromboxane A2 receptor antagonist), we measured human platelet-rich plasma (PRP) aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid, and whole blood (WB) aggregation induced by ADP. The release of P-selectin, transforming growth factor-beta 1, and the formation of thromboxane A2 in response to agonists were also investigated. Inhibitory effects of 100 micromol/l aspirin, 10 micromol/l cilostazol and 1 micromol/l ramatroban on 5 micromol/l ADP-induced PRP aggregation were similar. However, aspirin strongly inhibited thromboxane A2 formation in response to 5 micromol/l ADP compared with other drugs. Inhibitory effects of 10 micromol/l cilostazol on PRP aggregation and the release of molecules were quite similar in responsiveness induced by the three agonists. Aspirin and cilostazol inhibited platelet aggregation in a concentration-dependent, non-linear fashion, while ramatroban inhibited linearly with increasing concentration. Anti-platelet effects of drugs having different pharmacological mechanisms were demonstrated clearly by measuring PRP aggregation induced by the three agonists, and by measuring WB aggregation that most probably reflects not only platelet-platelet interactions, but also platelet-leukocyte interactions, as well as the release of intraplatelet molecules.
为比较阿司匹林（一种环氧化酶抑制剂）、西洛他唑（一种磷酸二酯酶III抑制剂）和雷马曲班（一种特异性血栓素A2受体拮抗剂）的抗血小板作用特性，我们检测了由二磷酸腺苷（ADP）、胶原和花生四烯酸诱导的富含人血小板血浆（PRP）聚集，以及由ADP诱导的全血（WB）聚集。还研究了P-选择素、转化生长因子-β1的释放以及对激动剂反应时血栓素A2的形成。100 μmol/l阿司匹林、10 μmol/l西洛他唑和1 μmol/l雷马曲班对5 μmol/l ADP诱导的PRP聚集的抑制作用相似。然而，与其他药物相比，阿司匹林对5 μmol/l ADP反应时血栓素A2的形成有强烈抑制作用。10 μmol/l西洛他唑对三种激动剂诱导的PRP聚集和分子释放的抑制作用在反应性方面相当相似。阿司匹林和西洛他唑以浓度依赖性、非线性方式抑制血小板聚集，而雷马曲班随浓度增加呈线性抑制。通过检测三种激动剂诱导的PRP聚集，以及检测最可能不仅反映血小板-血小板相互作用，还反映血小板-白细胞相互作用以及血小板内分子释放的WB聚集，清楚地证明了具有不同药理机制的药物的抗血小板作用。
