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• 研究论文 • 上一篇    

L-精氨酸·L-门冬氨酸盐抑制血小板功能的可能途径

王银叶, 王超, 韩梅, 彭师奇, 赵明*   

  1. 北京大学药学院, 北京 100083
  • 收稿日期:2003-07-13 修回日期:2004-02-10 出版日期:2004-03-15 发布日期:2004-03-15
  • 通讯作者: 赵明*

The Potential Pathway of L-arginine·L-aspartate for Inhibition of Platelet Function

WANG Yin-ye, WANG Chao, HAN Mei, PENG Shi-qi, ZHAO Ming*   

  1. School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China
  • Received:2003-07-13 Revised:2004-02-10 Online:2004-03-15 Published:2004-03-15
  • Contact: ZHAO Ming*

摘要: 目的 L-精氨酸·L门冬氨酸盐具有抑制血小板聚集和血栓形成的作用, 本文观察它在体外对GP Iib/IIIa单抗FITC-PAC-1与洗涤家兔血小板结合的影响和体内给药对大鼠血小板活性物质的影响, 以探讨其作用机制.方法 用流式细胞仪测定抗体与活化血小板的结合; 用比色法测定血清NO浓度; 用放免法测定cAMP, TXA2PGI2水平. 结果 L-精氨酸·L门冬氨酸盐30 mg·kg-1灌胃给药,可明显增加大鼠血浆NO浓度和大鼠主动脉段体外培养上清液中6-keto-PGF1α水平, 但对血浆中TXB26-keto-PGF1α水平和血小板内cAMP的含量无明显影响, 而乙酰水杨酸则明显降低血清TXB26-keto-PGF1α水平. L-精氨酸·L门冬氨酸盐100 μmol·L-1在体外可明显减少GP Iib/IIIa单抗FITC-PAC-1与血小板的结合. 结论 L-精氨酸·L-门冬氨酸盐抑制血小板聚集和抗血栓形成的功效可能通过增加血管内皮细胞释放NOPGI2,继而阻止血小板活化来介导,而与花生四烯酸及cAMP代谢途径无密切关系.

关键词: L-精氨酸·L门冬氨酸盐, 一氧化氮, 前列环素, 血栓素, 环腺苷一磷酸, 糖蛋白IIbIIIa单抗

Abstract: Aim L-Arginine·L-aspartate, a double salt, has been recently reported to inhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This study was conducted to investigate its effect on FITC-PAC-1, an anti-glycoprotein Iib/IIIa monoclonal antibody binding to activated platelets, and on correlative autacoid levels in plasma or in platelets in order to explore its potential pathway of inhibiting platelet aggregation and thrombosis. Methods Monoclonal antibody binding to activated platelets was assayed by flow cytometry; NO was assessed by colorimetric method.cAMP, TXB2 or 6-keto-PGF1α levels were assessed by radioimmunoassay. Results Gavaged 30 mg·kg-1 of L-arginine·L-aspartate increased both concentration of NO in plasma and 6-keto-PGF1α in incubated supernatant of aortic segment of rats ex vivo (P<0.05), but it did not influence cAMP content in platelets and the level of TXB2 or 6-keto-PGF1α in plasma of rats, whereas ASA significantly lowered TXB2 or 6-keto-PGF1α in plasma.Both 100 μmol·L-1 of L-arginine·L-aspartate and ASA inhibited FITC-PAC-1 binding to activated platelets in vitro. Conclusion The increase in NO and PGI2 release from endothelial cells and consequent inhibition of platelet activation may contribute to the inhibition of platelet aggregation and thrombosis by L-arginine·L-aspartate; whereas arachidonic acid or cAMP metabolic pathway is not closely correlative with the studied effect.

Key words: L-arginine·L-aspartate, L-arginine·L-aspartate, nitric oxide, nitric oxide, PGI2, PGI2, TXA2, TXA2, cAMP, cAMP, glycoprotein IIb/IIIa monoclonal antibody, glycoprotein IIb/IIIa monoclonal antibody

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Supporting: *Corresponding author. Tel.: 010-82802274