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自由基诱导的实验性血栓形成模型。在阿司匹林及其他不同物质中的应用。

Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances.

作者信息

Jourdan A, Aguejouf O, Imbault P, Doutremepuich F, Inamo J, Doutremepuich C

机构信息

Laboratoire d'Hématologie, Bordeaux, France.

出版信息

Thromb Res. 1995 Jul 1;79(1):109-23. doi: 10.1016/0049-3848(95)91519-q.

Abstract

A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.

摘要

大量实验研究表明,氧自由基在缺血再灌注过程中观察到的心肌损伤发病机制中起主要作用。本研究的目的是确定氧自由基是否能诱导血栓形成。为此,我们建立了一种新的实验性血栓形成模型。在全身注射不同剂量的孟加拉玫瑰红后,用汞灯发出的绿色滤光照射大鼠肠系膜小动脉不同时间,可实现可重复的局灶性血栓形成。然后测量血液中清除的栓子数量(N)、完全阻塞的持续时间(T)和每分钟的栓子数量。作为对照,不注射孟加拉玫瑰红,仅将血管暴露于滤光下。与该对照相比,结果清楚地表明自由基总是能诱导血栓形成,且诱导形成的血栓主要由血小板组成。在这种由自由基诱导的新血栓形成模型中,测试了抗血栓药物(阿司匹林,200mg/Kg,肝素,2mg/Kg)和抗氧化剂(维生素C,10和20mg/Kg,别嘌呤醇,200和300mg/Kg,维生素E,500和1000mg/Kg)。结果表明,只有肝素和维生素E对自由基诱导的血栓形成有抗血栓作用。该模型在研究不同药物的作用方面应是有用的,并可能为缺血性意外及其他心血管疾病带来新的治疗方式。

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