Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.
Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.
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阿司匹林在体内抑制血管纤溶酶原激活剂活性。
DOI：
10.1172/jci111454
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Rifkin,DB
中科院分区：
文献类型：
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作者：
Levin,RI;Harpel,PC;Weil,D;Chang,TS;Rifkin,DB
血管或组织型纤溶酶原激活剂（TPA）是生理性纤维蛋白溶解的关键酶。为了研究前列腺素在体内调节 TPA 合成和释放的作用，我们前瞻性研究了阿司匹林 (650 mg/d X 2) 对 13 名受试者在前臂静脉闭塞 10 分钟前后的 TPA 活性的影响。 TPA 活性通过新开发的酶联免疫吸附测定进行定量，该测定可测量并区分 TPA 和尿激酶 (UK) 样纤溶酶原激活剂活性。该测定基于这样的观察：Reptilase凝结的血浆中α2-纤溶酶抑制剂-纤溶酶复合物的浓度与添加的激活剂的量成比例线性增加。女性静息 TPA 活性高于男性（0.56 +/- 0.59 vs. 0.15 +/- 0.11 U/ml，P = 0.049）。静脉阻塞导致女性 TPA 活性增加 8 倍（至 4.5 U/ml，P = 0.006），男性 TPA 活性增加 15 倍（至 2.28 U/ml，P = 0.004），而未检测到 UK 活性。阿司匹林可抑制静脉阻塞后 TPA 活性的上升，男性抑制率达 69%（P = 0.004），女性抑制率达 70%（P = 0.014）。相比之下，阿司匹林对闭塞前或闭塞后血细胞比容或因子 VIII 相关抗原水平没有影响。血浆水杨酸水平与 TPA 抑制百分比之间不存在相关性。外源性阿司匹林（0-1微克/ml）和水杨酸盐（0-70微克/ml）均不会抑制外源性TPA产生α2-纤溶酶抑制剂-纤溶酶复合物，也不会干扰测定系统。我们得出的结论是，阿司匹林可能对人体具有以前未曾描述过的抗纤维蛋白溶解作用。
Vascular or tissue-type plasminogen activator (TPA) is a key enzyme in physiologic fibrinolysis. To study the role of prostaglandins in modulating the synthesis and release of TPA in vivo, we prospectively studied the effect of aspirin (650 mg/d X 2) on TPA activity in 13 human subjects before and after 10 min of forearm venous occlusion. TPA activity was quantified by a newly developed enzyme-linked immunosorbent assay that both measures and differentiates between TPA and urokinase (UK)-like plasminogen activator activity. This assay is based on the observation that the concentration of alpha 2-plasmin inhibitor-plasmin complexes in Reptilase-clotted plasma increases linearly in proportion to the amount of activator added. Resting TPA activity was higher in women than in men (0.56 +/- 0.59 vs. 0.15 +/- 0.11 U/ml, P = 0.049). Venous occlusion induced an eightfold rise in TPA activity in women (to 4.5 U/ml, P = 0.006) and a 15-fold rise in men (to 2.28 U/ml, P = 0.004), whereas UK activity was not detected. Aspirin inhibited the rise in TPA activity after venous occlusion by 69% in men (P = 0.004) and 70% in women (P = 0.014). In contrast, aspirin had no effect on pre- or post-occlusion hematocrits or Factor VIII-related antigen levels. There was no correlation between plasma salicylate level and percentage inhibition of TPA. Neither exogenous aspirin (0-1 microgram/ml) nor salicylate (0-70 micrograms/ml) inhibited the generation of alpha 2-plasmin inhibitor-plasmin complexes by exogenous TPA or interfered with the assay system. We conclude that aspirin may have an antifibrinolytic effect in man that has not been previously described.