血小板聚集的药理性解聚

PHARMACOLOGICAL DEAGGREGATION OF PLATELET AGGREGATION

在进行中的不可逆聚集的富血小板血浆(PRP)中,加入不同浓度的解聚剂,测定其解聚程度。以一系列作用机制不同的血小板解聚剂对ADP、胶原、花生四烯酸、U_(46619)(血栓素A_2类似物)、PAF所诱发的血小板聚集的拮抗作用的结果显示,血小板聚集作用得以维持是一个复杂的过程,涉及多种机制的参与,并和促聚剂种类有关。维持ADP诱发的聚集,需要外源性Ca^(2+)及细胞内Ca^(2+)的动员。PAF U_(46619)和花生四烯酸诱发的聚集作用的维持也需要细胞内钙的动员。但是胶原诱发的聚集作用的维持,有除Ca^(2+)、ADP以外的其他途径。维持持续的聚集并不依赖于血小板TXA_2(血栓素A_2)的持续合成,钙调节蛋白在血小板的持续聚集中起重要作用。钙调蛋白抑制剂都是有效的血小板解聚剂。各种血小板解聚剂的拮抗效果取决于(1) 采用促聚剂的种类、(2) 加入解聚剂时血小板聚集的时相、(3) 解聚剂的种类。

Antagonists of increasing concentrations were added to PRP which had exhibited irreversible aggregation and the extent of deaggregation was determined. Several classes of platelet antagonists with different mechanisms have been undertaken to reverse platelet aggregation induced by ADP, collagen, arachidonic acid, U_(46619) and PAF. The results indicate that maintenance of platelet aggregation is a complex phenomenon involving multiple mechanisms which depend on agonists. Maintenance of ADP induced aggregation requires exogenous calcium and active intracellular calcium mobilization. Active intracellular calcium mobilization appears to be essential for maintaining aggregation by PAF, U_(46619) and arachidonic acid. But additional pathway may be operative in maintaining collagen-induced aggregation. Calmodulin inhibitors with multiple actions are effective deaggregators. Calmodulin plays a role in maintaining platelet aggregation. The present study indicates that the ability of various antagonists to reverse platelet aggregation is closely related to three factors: 1) agonists used to stimulate platelet, 2) the time period following the initiation of platelet aggregation and, 3) the kinds of antagonists used.