González-Correa J A, Muñoz-Marín J, López-Villodres J A, Navas M D, Guerrero A, Torres J A, De La Cruz J P
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain.
Pharmacol Res. 2007 Aug;56(2):168-74. doi: 10.1016/j.phrs.2007.05.006. Epub 2007 Jun 6.
The aim of this study was to characterize the influence of the interaction between acetylsalicylic acid (ASA) and salicylic acid (SA) on the inhibition by ASA of platelet aggregation in platelets isolated from whole blood, and to determine whether leukocytes influence this pharmacological interaction. This in vitro study was done in human blood from which we prepared samples of whole blood, platelet-rich plasma (PRP), PRP plus mononuclear leukocytes, and PRP plus neutrophils. The variables recorded were maximum platelet aggregation intensity, thromboxane B2 (TxB2) production, and nitric oxide (NO) production (N=10 different samples in each type of experiment). Different concentrations of ASA and SA were incubated with all samples. In PRP, the concentration of ASA that inhibited maximum aggregation by 50% (IC50) (281+/-16microM) increased with increasing SA concentration to a maximum of more than 2mM when 500microM SA was used. In whole blood, the IC50 for ASA (24.9+/-1.2microM) decreased with decreasing SA concentrations to 7.9+/-0.8microM with 50microM SA and 15.6+/-0.9microM with 125microM SA, and increased to 46.2+/-2.6microM with 250microM SA and 96.3+/-7.2microM with 500microM SA. In experiments with PRP+neutrophils the IC50 of ASA increased in the presence of all concentrations of SA. The antagonistic interactions were also reflected in the changes in TxB2 production in all samples. In samples of neutrophils incubated with ASA, the curve for NO production was shifted to the right, a finding that paralleled the changes in platelet aggregation. In conclusion, the influence of the interaction between ASA and its metabolite SA on platelet aggregation difference depending on the type of sample, and was antagonistic in PRP but partially agonistic in whole blood. Nitric oxide synthesis showed an additive effect of the two compounds.
本研究的目的是描述乙酰水杨酸（ASA）与水杨酸（SA）之间的相互作用对从全血中分离的血小板中ASA抑制血小板聚集的影响，并确定白细胞是否影响这种药理相互作用。这项体外研究使用了人体血液，从中制备了全血、富血小板血浆（PRP）、PRP加单核白细胞以及PRP加中性粒细胞的样本。记录的变量包括最大血小板聚集强度、血栓素B2（TxB2）生成量以及一氧化氮（NO）生成量（每种类型的实验中N = 10个不同样本）。将不同浓度的ASA和SA与所有样本一起孵育。在PRP中，抑制最大聚集50%（IC50）的ASA浓度（281±16μM）随着SA浓度的增加而增加，当使用500μM SA时，最大值超过2mM。在全血中，ASA的IC50（24.9±1.2μM）随着SA浓度的降低而降低，使用50μM SA时降至7.9±0.8μM，使用125μM SA时降至15.6±0.9μM，使用250μM SA时升至46.2±2.6μM，使用500μM SA时升至96.3±7.2μM。在PRP + 中性粒细胞的实验中，在所有浓度的SA存在下，ASA的IC50均增加。拮抗相互作用也反映在所有样本中TxB2生成量的变化上。在用ASA孵育的中性粒细胞样本中，NO生成曲线向右移动，这一发现与血小板聚集的变化平行。总之，ASA与其代谢产物SA之间的相互作用对血小板聚集的影响因样本类型而异，在PRP中具有拮抗作用，但在全血中部分具有激动作用。一氧化氮合成显示出这两种化合物的加和效应。
