一个新合成的新木脂素类化合物W007B的抗血栓作用

doi:10.5246/jcps.2014.11.096

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (11): 760-764.DOI: 10.5246/jcps.2014.11.096

一个新合成的新木脂素类化合物W007B的抗血栓作用

胡琨¹, 刘晓岩¹, 朱元军¹, 张精亮¹, 刘晔², 王银叶^1*

1. 北京大学医学部分子与细胞药理学系, 北京 100191
2. 北京红惠新药科技有限公司, 北京 102600

收稿日期:2014-05-12 修回日期:2014-05-27 出版日期:2014-11-24 发布日期:2014-06-06
通讯作者: Tel.: 86-10-82802652, Fax: 86-10-62015584
基金资助:
Natural Science Foundation of China (Grant No. 81302763) and Beijing Natural Science Foundation (Grant No. 7144218).

Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo

Kun Hu¹, Xiaoyan Liu¹, Yuanjun Zhu¹, Jingliang Zhang¹, Ye Liu², Yinye Wang^1*

1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Beijing Honghui New Medical Technology Co. Ltd., Beijing 102600, China

Received:2014-05-12 Revised:2014-05-27 Online:2014-11-24 Published:2014-06-06
Contact: Tel.: 86-10-82802652, Fax: 86-10-62015584
Supported by:
Natural Science Foundation of China (Grant No. 81302763) and Beijing Natural Science Foundation (Grant No. 7144218).

摘要/Abstract

摘要：

W007B是一个新合成的新木脂素类衍生物。本研究利用不同的体内、体外模型观察它对血小板聚集和血栓形成的作用。用ADP、凝血酶、花生四烯酸和胶原为诱导剂, 进行体外血小板聚集实验。分别用动静脉旁路血栓模型、电刺激颈总动脉血栓形成模型、急性肺栓塞模型和尾出血实验评价W007B对动脉血栓形成的作用。实验结果显示: W007B对ADP、凝血酶、胶原、花生四烯酸诱导的血小板聚集均有抑制作用, IC₅₀分别是899.5 μM, 212.9 μM, 266.0 μM, 52.5 μM; W007B (2-10 mg/kg, ig) 单次给药可明显减轻大鼠动静脉旁路血栓重量; 显著延长大鼠电刺激颈总动脉血栓形成时间。W007B (2.8-14 mg/kg, ig) 单次给药明显降低ADP诱导的小鼠急性肺栓塞的死亡率; 显著延长小鼠尾出血时间。这些结果表明: W007B对多种诱导剂诱导的血小板聚集均有抑制作用, 其中对花生四烯酸诱导的血小板聚集抑制作用最强; W007B在多种动脉血栓形成模型上都有较强的抗血栓作用, 可作为新的抗血栓候选药进一步研发。

关键词: 抗血小板, 抗血栓, W007B

Abstract:

In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate (ADP), thrombin, arachidonic acid (AA) and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an IC₅₀ value of899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B (2–10 mg/kg, ig) significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8–14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.

Key words: Antiplatelet, Antithrombosis, W007B

中图分类号:

R962

Supporting:

胡琨, 刘晓岩, 朱元军, 张精亮, 刘晔, 王银叶. 一个新合成的新木脂素类化合物W007B的抗血栓作用[J]. 中国药学(英文版), 2014, 23(11): 760-764.

Kun Hu, Xiaoyan Liu, Yuanjun Zhu, Jingliang Zhang, Ye Liu, Yinye Wang. Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(11): 760-764.

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一个新合成的新木脂素类化合物W007B的抗血栓作用

Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo

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