Iacoviello L, De Curtis A, D'Adamo M C, Amore C, Buczko W, De Gaetano G, Donati M B
Laboratory of Thrombosis Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Italy.
Am J Physiol. 1994 Feb;266(2 Pt 2):H429-34. doi: 10.1152/ajpheart.1994.266.2.H429.
The role of vascular cyclooxygenase pathway on tissue-type plasminogen activator (t-PA) release after venous occlusion was studied in anesthetized rats. After the inferior vena cava was clamped for 30 min, fibrinolytic activity increased from 143.7 +/- 14.5 to 209.5 +/- 10.3 mm2 (mean +/- SE, P < 0.002). This increase was prevented by aspirin at high (100 mg/kg i.v.) but not at low doses (1 mg/kg i.v.). Dazoxiben (10 mg/kg i.v.), an inhibitor of thromboxane synthase, was ineffective on the fibrinolytic response. Both the basal levels of 6-ketoprostaglandin F1 alpha and its increase after venous occlusion were suppressed by 100 mg/kg aspirin administration (from 0.64 +/- 0.2 to 0.05 +/- 0.002 ng/ml before occlusion, P < 0.001; and from 1.08 +/- 0.2 to 0.06 +/- 0.002 ng/kg after occlusion, P < 0.001), whereas they were both unaffected by aspirin at low doses (from 0.53 +/- 0.06 before to 1.20 +/- 0.08 ng/ml after stasis). Moreover, iloprost, a stable analogue of prostacyclin, reversed the aspirin inhibitory effects on fibrinolytic activity by restoring t-PA vascular release after venous stasis. Our results provide experimental evidence that an intact cyclooxygenase pathway in vascular wall is required for the fibrinolytic activity increase after venous occlusion in rats.
在麻醉大鼠中研究了血管环氧化酶途径在静脉闭塞后组织型纤溶酶原激活物（t-PA）释放中的作用。下腔静脉夹闭30分钟后，纤溶活性从143.7±14.5增加至209.5±10.3平方毫米（平均值±标准误，P<0.002）。高剂量阿司匹林（静脉注射100毫克/千克）可阻止这种增加，但低剂量（静脉注射1毫克/千克）则不能。血栓素合酶抑制剂达唑昔班（静脉注射10毫克/千克）对纤溶反应无效。静脉注射100毫克/千克阿司匹林可抑制6-酮前列环素F1α的基础水平及其在静脉闭塞后的增加（闭塞前从0.64±0.2降至0.05±0.002纳克/毫升，P<0.001；闭塞后从1.08±0.2降至0.06±0.002纳克/千克，P<0.001），而低剂量阿司匹林对其均无影响（淤滞后从0.53±0.06升至1.20±0.08纳克/毫升）。此外，前列环素的稳定类似物伊洛前列素通过恢复静脉淤滞后t-PA的血管释放，逆转了阿司匹林对纤溶活性的抑制作用。我们的结果提供了实验证据，表明大鼠静脉闭塞后纤溶活性增加需要血管壁中完整的环氧化酶途径。
