银杏二萜内酯A,B,K抗血小板聚集作用机制研究

Effects of ginkgolide A,B and K on platelet aggregation

为研究银杏二萜内酯A,B,K(GA,GB,GK)对家兔血小板聚集功能的影响,比较三者作用机制的异同及强弱,该研究采用体外实验法,观察不同剂量GA,GB,GK对血小板活化因子(PAF)诱导家兔血小板聚集作用的影响。研究结果显示,3种银杏二萜内酯均可抑制PAF诱导的体外家兔血小板聚集,其强弱顺序为GK>GB>GA;三者还能够拮抗[~3H]PAF与PAF受体的特异性结合,拮抗能力同样为GK>GB>GA。进一步研究三者对于PAF诱导后血小板中胞内[Ca^(2+)]i动员及胞内c AMP水平的变化,发现三者均能够剂量依赖性的抑制胞内[Ca^(2+)]i动员并提高胞内c AMP水平,且它们的作用强弱与拮抗PAF受体能力的强弱一致。表明银杏二萜内酯GK对于PAF受体具有高度的选择性,并能够通过激活c AMP信号通路、抑制胞内[Ca^(2+)]i动员的方式达到抑制血小板聚集的目的,GB、GA对PAF受体也有较强的拮抗作用,但弱于GK。

To investigate the effects of ginkgolide A （GA）, ginkgolide B （GB） and ginkgolide K （GK） on platelet aggregation in rabbits, and compare the similarities and differences among these three components. The effects of different doses of ginkgolide A, B and K on platelet aggregation induced by platelet activating factor （PAF） were observed by using in vitro experiment. The results showed that three compounds could inhibit platelet aggregation induced by PAF in vitro, and the intensity was GK 〉 GB 〉 GA. It was further found that all of them can mobilize[Ca2＋]i and enhance intracellular c-AMP level in a dose-dependent manner, which was consistent to the ability to antagonize PAF receptor. These findings indicated that GK was highly selective for PAF receptor, and may inhibit platelet aggregation by activating cAMP signaling pathway and inhibiting intracellular[Ca2＋]i mobilization; GB and GA also had strong antagonism to PAF receptor, but the effect was weaker than that of GK.