ADP Plays a Key Role in Thrombogenesis in Rats-猫眼课题宝

ADP 在大鼠血栓形成中发挥关键作用

DOI：

发表时间：

1988

期刊：

Thrombosis and Haemostasis

影响因子：

6.7

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

J. Maffrand;A. Bernat;D. Delebassée;G. Defreyn;Cazenave Jp;J. Gordon

通过口服给药后比较两种ADP诱导的血小板聚集抑制剂的作用，评价了ADP、花生四烯酸代谢物和5-羟色胺作为大鼠血栓形成因子的相对重要性（噻氯匹定和PCR 4099），三种环氧合酶抑制剂（阿司匹林、三氟柳和吲哚布芬）和选择性5-羟色胺5 HT 2受体拮抗剂（酮色林）对血小板聚集，在四个血小板依赖性血栓形成模型和出血时间。噻氯匹定和PCR 4099可完全抑制ADP和胶原诱导的血小板聚集，而环氧合酶抑制剂仅抑制胶原聚集。酮色林或利血平消耗血小板5-羟色胺不影响血小板聚集。噻氯匹定和PCR 4099显著延长大鼠断尾出血时间。这可能与其已知的抑制ADP介导的血小板聚集的能力有关。相反，环氧合酶抑制剂根本不影响出血时间。利血平和酮色林通过干扰5-羟色胺对血管壁的作用而延长出血时间。噻氯匹定和PCR 4099在所有模型中均为非常有效的抗血栓形成剂。阿司匹林，只有在高剂量，抑制血栓形成的丝线在动静脉分流，这表明抑制环氧合酶是不负责。三氟柳在所有模型中均无活性，而吲哚布芬略微减少丝线和金属线圈模型中的血栓形成。酮色林和利血平仅在金属弹簧圈模型中减少血栓。血栓形成大大减少了小鹿帽大鼠，缺乏ADP在其血小板致密颗粒，因为遗传储存池缺陷。总之，药物和小鹿帽大鼠的结果支持ADP在大鼠血栓形成中起关键作用的概念。

Summary The relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.

ADP-dependent common receptor mechanism for binding of von Willebrand factor and fibrinogen to human platelets.