白藜芦醇在体外对ADP诱导人血小板聚集的抑制作用及其机制

白藜芦醇(resveratrol，RESV)是一类广泛存在于葡萄、何首乌、花生等多种天然植物中的多酚类化合物。本研究观察RESV在体外对腺苷二磷酸(adenosine diphosphate，ADP)诱导健康志愿者血小板聚集、血小板膜结合纤维蛋白原(platelet membrane-bound fibrinogen，PFig)的抑制作用及其机制。应用血小板聚集仪、流式细胞仪及蛋白印迹技术(Western blotting)，研究RESV和磷脂酶Cβ抑制剂(phospholipase Cβ inhibitor，U73122)对ADP诱导的健康志愿者血小板聚集、PFig及血小板磷酸化磷脂酶Cβ3(phospho-phospholipase Cβ3，P-PLCβ3)和总磷脂酶Cβ3(total-phospholipase Cβ3，T-PLCβ3)蛋白表达的影响。与对照组相比，RESV(终浓度分别为25、50和100 μmol·L^-1)剂量依赖性地抑制ADP诱导的血小板聚集及Pfig、RESV与U73122对血小板聚集及PFig的抑制有叠加作用。RESV(终浓度为50 μmol·L^-1)还降低血小板P-PLCβ3蛋白的表达，降低血小板P-PLCβ3/T-PLCβ3的表达比率。RESV可能通过抑制健康志愿者血小板磷脂酶Cβ(phospholipase Cβ，PLCβ)的活性，降低了ADP诱导的血小板聚集及PFig，提示RESV有明确的抗血小板作用，具有新型抗血栓药物的研究前景。

Suppressive effect in vitro of resveratrol on ADP induced human platelet aggregation and its active mechanism

Resveratrol (RESV) is a polyphenolic compound existed in native plants such as grape, fleeceflower root, and peanut, etc. The aim of this study was to investigate the effects in vitro of RESV on adenosine diphosphate (ADP)-induced platelet aggregation, platelet membrane-bound fibrinogen (PFig) its mechanism of action. The effects of RESV and phospholipase Cbeta inhibitor (U73122) on ADP-induced healthy human volunteers platelet aggregation, PFig, and the expression of phospho-phospholipase Cbeta3 (P-PLCbeta3) and total-phospholipase Cbeta3 (T-PLCbeta3) were studied with platelet aggregometer, flow cytometry and Western blotting, respectively. Compared with control group, RESV at 25, 50 and 100 micromol x L(-1) inhibited ADP-induced platelet aggregation and PFig in a dose dependent manner, and RESV at 25 micromol x L(-1) obviously reduced expression of P-PLCbeta3 and ratio of P-PLCbeta3 to T-PLCbeta3 in platelet of healthy human volunteers. Furthermore, RESV and U73122 had additive effect in inhibiting platelet aggregation and PFig. All these suggested that RESV inhibited platelet aggregation and PFig induced by ADP partly through decreasing the activity of PLCbeta of platelets, and that RESV had definite effect of antiplatelet and might be developed as a novel antithrombotic agent.