Kawano K, Aoki I, Aoki N, Homori M, Maki A, Hioki Y, Hasumura Y, Terano A, Arai T, Mizuno H, Ishikawa K
Second Department of Internal Medicine, Kyorin University School of Medicine, Mitaka-city, Tokyo, Japan.
Am Heart J. 1998 Feb;135(2 Pt 1):268-71. doi: 10.1016/s0002-8703(98)70092-4.
The mechanisms that underlie reocclusion during thrombolytic therapy have not yet been clarified. The purpose of this study was to investigate the activating effects of tissue-type plasminogen activator and urokinase and the inhibitory effects of acetylsalicylic acid by measuring platelet surface P-selectin as a marker of platelet activation. After addition of urokinase (final concentration 192 U/ml, 1920 U/ml, or 19,200 U/ml) or tissue-type plasminogen activator (final concentration 120 U/ml, 1200 U/ml, or 12,000 U/ml) to platelet-rich plasma from 12 healthy persons, platelet surface P-selectin expression was measured by means of flow cytometry with an anti-CD62 monoclonal antibody. The presence of urokinase and tissue-type plasminogen activator increased platelet surface P-selectin expression in a concentration-dependent manner. In the next step, either 160 mg/day (n = 6) or 660 mg/day (n = 6) acetylsalicylic acid was administered to the 12 healthy persons, and venous blood samples were collected after 7 days of treatment. Platelet surface P-selectin expression was measured with the method used earlier and after addition of tissue-type plasminogen activator or urokinase. Although the effect of acetylsalicylic acid at 160 mg/day on P-selectin expression was minimal, a dose of 660 mg/day suppressed platelet P-selectin expression and inhibited the platelet activating effects of tissue-type plasminogen activator and urokinase in a statistically significant way. Platelets were activated by tissue-type plasminogen activator or urokinase, and this platelet activation was suppressed with administration of acetylsalicylic acid at 660 mg/day.
溶栓治疗期间再闭塞的潜在机制尚未阐明。本研究的目的是通过测量血小板表面P-选择素作为血小板活化的标志物，来研究组织型纤溶酶原激活剂和尿激酶的激活作用以及乙酰水杨酸的抑制作用。向12名健康人的富血小板血浆中加入尿激酶（终浓度192 U/ml、1920 U/ml或19200 U/ml）或组织型纤溶酶原激活剂（终浓度120 U/ml、1200 U/ml或12000 U/ml）后，用抗CD62单克隆抗体通过流式细胞术测量血小板表面P-选择素的表达。尿激酶和组织型纤溶酶原激活剂的存在以浓度依赖性方式增加血小板表面P-选择素的表达。在下一步中，12名健康人分别服用160 mg/天（n = 6）或660 mg/天（n = 6）的乙酰水杨酸，治疗7天后采集静脉血样本。用之前使用的方法并在加入组织型纤溶酶原激活剂或尿激酶后测量血小板表面P-选择素的表达。虽然160 mg/天的乙酰水杨酸对P-选择素表达的影响最小，但660 mg/天的剂量可抑制血小板P-选择素的表达，并以统计学上显著的方式抑制组织型纤溶酶原激活剂和尿激酶的血小板激活作用。血小板被组织型纤溶酶原激活剂或尿激酶激活，而660 mg/天的乙酰水杨酸给药可抑制这种血小板激活。
