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丁基苯酞对大鼠血栓形成及血小板功能的影响

EFFECTS OF 3-N-BUTYLPHTHALIDE ON THROMBOSIS FORMATION AND PLATELET FUNCTION IN RATS

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【作者】 徐皓亮冯亦璞

【Author】 XU Hao liang, FENG Yi pu (Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China)

【机构】 中国医学科学院、中国协和医科大学药物研究所!北京100050

【摘要】 目的 研究消旋、左旋和右旋丁基苯酞 (dl ,l 和d NBP)对血栓形成及血小板功能的影响。方法 利用半体外血栓形成术及比浊法 ,观察dl ,l 和d NBP及阿司匹林 (Asp)对大鼠血栓湿重和血小板聚集率的影响 ,并用放免法、荧光分光光度法测定其对血小板内cAMP和TXB2 的水平以及血小板 5 HT释放率的影响。结果 ip ,dl NBP和l NBP可剂量依赖性地抑制大鼠血栓形成 ,且l NBP作用与Asp相似 ,d NBP对半体外血栓形成无显著作用 ;dl ,d 和l NBP可显著抑制胶原、ADP、花生四烯酸诱导的血小板聚集。结论 NBP有抗血栓作用 ,l NBP作用最强 ,dl NBP作用较弱 ,其抗栓作用与升高血小板内cAMP的含量及抑制 5 HT释放有关

【Abstract】 AIM To study the effects of dl , l and d 3 n butylphthalide (NBP) on platelet aggregation and thrombus formation. METHODS Thrombus formation was assessed by silk thread induced thrombosis in arteriovenous shunt in rats. Rat platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), collagen and thrombin was detected in vitro . The generation of thromboxane B 2 (TXB 2) and the concentration of cAMP in rabbit platelets in vitro were studied with radioimmunological assay. RESULTS dl , l NBP (5, 10, 20 mg·kg -1 ip) exhibited a dose dependent inhibitory effect on thrombus formation in rats, while d NBP was not active. dl , l , d NBP (3-100 μmol·L -1 ) inhibited platelet rich plasma aggregation in vitro induced by ADP, collagen and AA, and all of them showed no effect on thrombin induced platelet aggregation. In addition, dl , l NBP (10-100 μmol·L -1 ) were found to increase [cAMP]i in dose related fashion. In the meantime, only high concentration of l NBP was found to decrease platelet TXA 2 level. In addition, l NBP (1-100 μmol·L -1 ) showed significant effect on inhibiting 5 HT release from platelets. In contrast, dl and d NBP showed no effect. CONCLUSION The results suggest that NBP is a potent antiplatelet drug, the mechanism of its antithrombotic and antiplatelet activity is related to its regulation of cAMP level and 5 HT release.

【基金】 国家科委1035工程重大项目基金!(94 ZD 0 1);国家自然科学基金重大项目基金!(2 9790 12 2 )资助
  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2001年05期
  • 【分类号】R965
  • 【被引频次】95
  • 【下载频次】466
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