ANTITHROMBOTIC AND THROMBOLYTIC ACTIVITY OF SULODEXIDE IN RATS
ANTITHROMBOTIC AND THROMBOLYTIC ACTIVITY OF SULODEXIDE IN RATS
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DOI：
10.1007/bf02591420
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发表时间：
1992-08-01
期刊：
影响因子：
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通讯作者：
BABBINI, M
中科院分区：
文献类型：
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作者：
BARBANTI, M;GUIZZARDI, S;BABBINI, M
我们评估了舒洛地特，一种提取的糖胺多糖，在大鼠静脉血栓形成模型(腔静脉结扎术)中预防血栓形成和减少稳定血栓的能力。静脉血栓形成前10min注射舒洛地特呈剂量依赖性抑制血栓形成(半数有效剂量为0.55 mg/kg)。给6小时龄血栓的大鼠服用舒洛地特后，血栓大小明显缩小，最高剂量(2 mg/kg)给药2小时后血栓大小达到70%。舒洛地特对已建立的血栓的影响似乎至少部分是由于纤溶介导的机制，因为它被著名的抗纤溶药物epsilon-氨基己酸显著抑制。舒洛地特治疗对血浆纤溶酶原激活物及其特异性抑制物水平无明显影响。我们还显示，当给患有6小时血栓的动物注射荧光素标记的舒洛地特时，2小时后采集的血栓中存在荧光素标记的舒洛地特，但随后从血液中消失。荧光主要位于充满无定形物质的区域，经磷钨酸-苏木素染色鉴定为纤维蛋白。在单独使用荧光素的大鼠中，没有检测到荧光素标记物质。这些发现表明，除了预防静脉血栓的形成外，舒洛地特还能够促进血栓的溶解，其机制部分与局部纤溶刺激有关。
We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis-mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation.