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吲哚布芬的抗凝血活性,一种抗血小板药物。

Anticoagulant Activities of Indobufen, an Antiplatelet Drug.

机构信息

Department of Marketing, Hangzhou Zhongmei Huadong Pharmaceutical Company, Hangzhou 310011, China.

State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Molecules. 2018 Jun 15;23(6):1452. doi: 10.3390/molecules23061452.

Abstract

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in rabbit plasma. We evaluated the anticoagulant mechanisms on the content of the platelet factor 3,4 (PF3,4), and the coagulation factor 1, 2, 5, 8, 10 (FI, II, V, VIII, X) in rabbits, as well as the in vivo bleeding time and clotting time in mice. The pharmacodynamic differences between indobufen and warfarin sodium, rivaroxaban, and dabigatran were further studied on thrombus formation and the content of FII and FX in rats. Animal experiments showed that intragastric-administrated indobufen can significantly reduce the APTT, PT, TT, PF3, FI, II, V, VIII, and X plasma contents. Its inhibitory effect on plasma FII was better than thrombin inhibitor dabigatran with effect on FX better than FXa inhibitor rivaroxaban. These results suggest that indobufen has some anticoagulant effects as strong as some conventional anticoagulants. The mechanism may be related to both exogenous and endogenous coagulation system.

摘要

吲哚布芬是一种新型抗血小板聚集药物,但关于其抗凝作用的研究还不够充分。在本研究中,通过监测兔血浆中活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和凝血酶时间(TT)来确定吲哚布芬的抗凝活性。我们评估了血小板因子 3、4(PF3、4)含量以及凝血因子 1、2、5、8、10(FI、II、V、VIII、X)在兔体内的抗凝机制,以及在小鼠体内的出血时间和凝血时间。进一步研究了吲哚布芬与华法林钠、利伐沙班和达比加群在血栓形成和大鼠 FII 和 FX 含量方面的药效学差异。动物实验表明,灌胃给予吲哚布芬可显著降低 APTT、PT、TT、PF3、FI、II、V、VIII 和 X 血浆含量。其对血浆 FII 的抑制作用优于凝血酶抑制剂达比加群,对 FX 的作用优于 FXa 抑制剂利伐沙班。这些结果表明,吲哚布芬具有与一些常规抗凝剂相当的抗凝作用。其作用机制可能与外源性和内源性凝血系统有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1198/6099839/b6b4123c5693/molecules-23-01452-g001.jpg

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