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口服硫酸皮肤素可减少体内静脉血栓形成:作为静脉血栓栓塞形成制剂的潜在用途。

Oral administration of dermatan sulphate reduces venous thrombus formation in vivo: potential use as a formulation for venous thromboembolism.

机构信息

CSIRO, Agriculture and Food, Queensland Bioscience Precinct, 306 Carmody Road, St Lucia, QLD, 4067, Australia.

Centre for Clinical Research, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, QLD, 4029, Australia.

出版信息

Inflammopharmacology. 2021 Apr;29(2):525-535. doi: 10.1007/s10787-020-00771-x. Epub 2020 Nov 23.

Abstract

Dermatan sulphate (DS) is a sulphated polysaccharide that displays complexity in constituent sulphated disaccharides and interacts with proteins and signalling molecules to modulate numerous biological processes, including inhibition of the coagulation cascade and regulation of blood clotting and fibrinolysis. This study shows the antithrombotic and anticoagulant effects of DS prepared from bovine collagen waste liquor following oral and intravenous administrations in a deep vein thrombosis (DVT) rabbit model. In vitro, the prothrombin time, activated partial thromboplastin time, and thrombin citrated plasma clotting assays revealed that bovine DS had strong antithrombotic and anticoagulant effects comparable to low-molecular-weight heparin [Clexane (enoxaparin sodium)]. In a DVT rabbit model, animals received intravenous and oral administrations of bovine DS and Clexane providing further evidence that both agents had strong antithrombotic and anticoagulant effects by significantly reducing or preventing clot formation. Thromboelastography (TEG) assays revealed further that both bovine DS and Clexane substantially prolonged the clotting time of recalcified citrated whole blood, but only bovine DS could retain clot strength suggesting that bovine DS had less effect on platelet-fibrin interactions. In conclusion, this is the first report that oral administration of DS from bovine collagen waste liquor reduces experimental venous thrombus formation warranting further research into bovine DS as an oral antithrombotic therapeutic.

摘要

硫酸皮肤素(DS)是一种硫酸化多糖,其组成的硫酸化二糖具有复杂性,并与蛋白质和信号分子相互作用,从而调节多种生物过程,包括抑制凝血级联反应以及调节血液凝固和纤维蛋白溶解。本研究展示了从牛胶原蛋白废液中制备的 DS 在深静脉血栓形成(DVT)兔模型中经口服和静脉给药的抗血栓和抗凝作用。体外,凝血酶原时间、活化部分凝血活酶时间和凝血酶柠檬酸血浆凝固测定显示,牛 DS 具有很强的抗血栓和抗凝作用,与低分子量肝素 [Clexane(依诺肝素钠)] 相当。在 DVT 兔模型中,动物接受牛 DS 和 Clexane 的静脉和口服给药,进一步证明这两种药物均通过显著减少或预防血栓形成而具有很强的抗血栓和抗凝作用。血栓弹力图(TEG)测定进一步表明,牛 DS 和 Clexane 均可显著延长复钙柠檬酸全血的凝固时间,但只有牛 DS 可保持血凝块强度,表明牛 DS 对血小板-纤维蛋白相互作用的影响较小。总之,这是首个报道口服牛胶原蛋白废液 DS 可减少实验性静脉血栓形成的报告,这证明牛 DS 作为口服抗血栓治疗具有进一步研究的价值。

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