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硫酸皮肤素和肝素作为抗血栓形成剂的相对疗效的实验研究。

Experimental studies on the relative efficacy of dermatan sulphate and heparin as antithrombotic agents.

作者信息

Merton R E, Thomas D P

机构信息

National Institute for Biological Standards and Control, London, U.K.

出版信息

Thromb Haemost. 1987 Oct 28;58(3):839-42.

PMID:3433248
Abstract

In this study, the anticoagulant and antithrombotic properties of unfractionated heparin (UFH) and dermatan sulphate (DS) were compared. The ability of UFH and DS to impair thrombin generation in vitro and in ex vivo plasma samples was also studied. DS has minimal anticoagulant activity by conventional assays but impairs thrombin generation both in vitro and in ex vivo plasma samples. However, thrombin generation could not be suppressed below about 35% of control values at all doses of DS studied. While this was sufficient to impair experimental venous thrombosis during 10 minutes' stasis, DS was ineffective in preventing thrombosis following 20 minutes' stasis in doses up to 1.25 mg/kg. In contrast, 1 microgram/ml of UFH completely suppressed thrombin generation in vitro, and 150 micrograms/kg prevented thrombogenesis over a period of 20 minutes' stasis. Neither drug prolonged the bleeding time (BT) at effective antithrombotic doses, but 2.5 mg/kg UFH significantly increased the BT, whereas DS did not. While DS has antithrombotic activity, it is less effective than UFH in inhibiting thrombin generation, and as an antithrombotic agent.

摘要

在本研究中,对普通肝素(UFH)和硫酸皮肤素(DS)的抗凝和抗血栓形成特性进行了比较。还研究了UFH和DS在体外及离体血浆样本中抑制凝血酶生成的能力。通过传统检测方法,DS的抗凝活性极小,但在体外及离体血浆样本中均能抑制凝血酶生成。然而,在所研究的所有DS剂量下,凝血酶生成均无法被抑制至对照值的约35%以下。虽然这足以在10分钟的血液淤滞期间损害实验性静脉血栓形成,但在长达20分钟的血液淤滞期间,剂量高达1.25 mg/kg的DS在预防血栓形成方面无效。相比之下,1微克/毫升的UFH在体外完全抑制了凝血酶生成,150微克/千克在20分钟的血液淤滞期间预防了血栓形成。在有效的抗血栓形成剂量下,两种药物均未延长出血时间(BT),但2.5 mg/kg的UFH显著延长了BT,而DS则没有。虽然DS具有抗血栓形成活性,但在抑制凝血酶生成方面不如UFH有效,作为抗血栓形成剂也是如此。

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