N~α-乙酰-精氨酰-甘氨酰-天冬氨酰-对甲氧基苯乙胺对血小板聚集的抑制

Effect of N~α-acetyl arginyl-glycyl-aspartyl-p-methoxyl phenylethylamine on platelet aggregation

Nα-乙酰 -精氨酰 -甘氨酰 -天冬氨酰 -对甲氧基苯乙胺 (W2 0 0 2 )是精 -甘 -天冬氨酸 (Arg- Gly- Asp)肽类血小板聚集抑制剂 .为探讨其抗血小板聚集的活性 ,分别用比浊法和血小板计数的方法测定二磷酸腺苷 (ADP)及高剪切速率诱导的血小板聚集 ,并用放射性配体分析法测定血小板表面结合 [12 5I]纤维蛋白原 (FGN)的含量 ,以了解 W2 0 0 2竞争性抑制 [12 5I]FGN与血小板糖蛋白 (GP) b/ a结合的生物活性 .结果显示 :W2 0 0 2有明显的抑制 ADP诱导血小板聚集的活性 ,除最低终浓度(9 μmol· L-1)外 ,其余各浓度点 (2 70 ,1 35,45μmol· L-1)与生理盐水对照组比较差异均非常显著 ;其对抗高剪切速率诱导的血小板聚集也有明确的量 -效关系 ;抑制 [12 5I]FGN与血小板结合的 IC50值为 (41 .5± 2 .9)μmol· L-1,在老年人和青年人群中比较无明显差异 .研究提示 W2 0 0 2通过抑制FGN与血小板 GP b/ a的结合而发挥作用 .

N α-Acetyl arginyl-glycyl-aspar- tyl-p-methoxyl phenylethylamine(W2002) is an analog of the RGD(Arg-Gly-Asp)containing peptide sequence that is recognized by the platelet membrane glucoprotein(GP)Ⅱb/Ⅲa receptor. To investigate the bioactivity of W2002 as an antiplatelet agent, turbidimetric method and platelet count were used to determine the platelet aggregation induced by adenosine diphosphate(ADP) and high shear rate, respectively. The results indicated that W2002 can inhibit platelet aggregation induced by ADP and high shear rate. The content of platelet membrane fibrinogen was detected by determining the bound radioactivity of [ 125I]fibrinogen in platelet pellet. W2002 blocked [ 125I]fibrinogen binding to platelet GPⅡb/Ⅲa〔IC 50=(41.5±2.9)μmol·L -1〕. Its activity has no significant difference between the old and young people. The results suggest that W2002 play its role of inhibition on platelet aggregation by suppressing the binding of fibrinogen to platelet membrane GPⅡb/Ⅲa.