丁基苯酞对大鼠血栓形成及血小板功能的影响

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。

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

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 B2 (TXB2) 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 i.p.) exhibited a dose-dependent inhibitory effect on thrombus formation in rats, while d-NBP was not active. dl, l, d-NBP (3-100 mumol.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 mumol.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 TXA2 level. In addition, l-NBP (1-100 mumol.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.