Spertini O, Hauert J, Bachmann F
Department of Medicine, University Hospital Center, Lausanne, Switzerland.
Thromb Haemost. 1992 Jan 23;67(1):126-30.
Platelet function defects observed in chronic alcoholics are not wholly explained by the inhibitory action of ethanol on platelet aggregation; they are not completely reproduced either in vivo by short-term ethanol perfusion into volunteers or in vitro by the addition of ethanol to platelet-rich plasma. As acetaldehyde (AcH) binds to many proteins and impairs cellular activities, we investigated the effect of this early degradation product of ethanol on platelets. AcH formed adducts with human platelets at neutral pH at 37 degrees C which were stable to extensive washing, trichloracetic acid hydrolysis and heating at 100 degrees C, and were not reduced by sodium borohydride. The amount of platelet adducts formed was a function of the incubation time and of the concentration of AcH in the reaction medium. At low AcH concentrations (less than 0.2 mM), platelet bound AcH was directly proportional to the concentration of AcH in the reaction medium. At higher concentrations (greater than or equal to 0.2 mM), AcH uptake by platelets tended to reach a plateau. The amount of adducts was also proportional to the number of exposures of platelets to pulses of 20 microM AcH. AcH adducts formation severely impaired platelet aggregation and shape change induced by ADP, collagen and thrombin. A positive correlation was established between platelet-bound AcH and inhibition of aggregation. SDS-PAGE analysis of AcH adducts at neutral pH demonstrated the binding of [14C]acetaldehyde to many platelet proteins. AcH adduct formation with membrane glycoproteins, cytoskeleton and enzymes might interfere with several steps of platelet activation and impair platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)
慢性酒精中毒患者中观察到的血小板功能缺陷不能完全用乙醇对血小板聚集的抑制作用来解释；在志愿者体内通过短期灌注乙醇或在体外向富含血小板的血浆中添加乙醇，都不能完全重现这些缺陷。由于乙醛（AcH）能与多种蛋白质结合并损害细胞活性，我们研究了乙醇的这种早期降解产物对血小板的影响。在37摄氏度中性pH条件下，AcH与人血小板形成加合物，这些加合物经大量洗涤、三氯乙酸水解和100摄氏度加热后仍稳定，且不能被硼氢化钠还原。形成的血小板加合物量是孵育时间和反应介质中AcH浓度的函数。在低AcH浓度（小于0.2 mM）时，血小板结合的AcH与反应介质中AcH浓度成正比。在较高浓度（大于或等于0.2 mM）时，血小板对AcH的摄取趋于达到平台期。加合物的量也与血小板暴露于20 microM AcH脉冲的次数成正比。AcH加合物的形成严重损害了由ADP、胶原和凝血酶诱导的血小板聚集和形状改变。血小板结合的AcH与聚集抑制之间建立了正相关。在中性pH条件下对AcH加合物进行SDS-PAGE分析表明，[14C]乙醛与许多血小板蛋白结合。AcH与膜糖蛋白、细胞骨架和酶形成加合物可能会干扰血小板活化的几个步骤并损害血小板聚集。（摘要截短于250字）
