Shen Ming Y, Hsiao George, Liu Chang L, Fong Tsorng H, Lin Kuang H, Chou Duen S, Sheu Joen R
Graduate Institute of Medical Sciences and Topnotch Stroke Research Centre, Taipei Medical University, Taipei, Taiwan.
Br J Haematol. 2007 Nov;139(3):475-85. doi: 10.1111/j.1365-2141.2007.06788.x. Epub 2007 Sep 14.
Resveratrol has been reported to have antiplatelet activity; however, the detailed mechanisms have not yet been resolved. This study aimed to systematically examine the detailed mechanisms of resveratrol in the prevention of platelet activation in vitro and in vivo. Resveratrol (0.05-0.25 micromol/l) showed stronger inhibition of platelet aggregation stimulated by collagen (1 microg/ml) than other agonists. Resveratrol (0.15 and 0.25 micromol/l) inhibited collagen-induced platelet activation accompanied by [Ca(+2)]i mobilization, thromboxane A(2) (TxA(2)) formation, phosphoinositide breakdown, and protein kinase C (PKC) activation. Resveratrol markedly increased levels of NO/cyclic guanosine monophosphate (GMP), and cyclic GMP-induced vasodilator-stimulated phosphoprotein phosphorylation. Resveratrol markedly inhibited p38 mitogen-activated protein kinase (MAPK) but not Jun N-terminal kinase or extracellular signal-regulated kinase-2 phosphorylation in washed platelets. Resveratrol-reduced hydroxyl radical (OH(-)) formation in the electron spin resonance study. In an in vivo study, resveratrol (5 mg/kg) significantly prolonged platelet plug formation of mice. In conclusion, the main findings of this study suggest that the inhibitory effects of resveratrol possibly involve (i) inhibition of the p38 MAPK-cytosolic phospholipase A(2)-arachidonic acid-TxA(2)-[Ca(+2)]i cascade and (ii) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C and/or PKC activation. Resveratrol is likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.
据报道，白藜芦醇具有抗血小板活性；然而，其详细机制尚未明确。本研究旨在系统研究白藜芦醇在体外和体内预防血小板活化的详细机制。白藜芦醇（0.05 - 0.25微摩尔/升）对胶原（1微克/毫升）刺激的血小板聚集的抑制作用强于其他激动剂。白藜芦醇（0.15和0.25微摩尔/升）抑制胶原诱导的血小板活化，同时伴有细胞内钙离子（[Ca(+2)]i）动员、血栓素A(2)（TxA(2)）形成、磷酸肌醇分解以及蛋白激酶C（PKC）活化。白藜芦醇显著增加一氧化氮/环磷酸鸟苷（cGMP）水平以及环磷酸鸟苷诱导的血管舒张刺激磷蛋白磷酸化。白藜芦醇显著抑制洗涤血小板中p38丝裂原活化蛋白激酶（MAPK）的磷酸化，但不影响Jun N末端激酶或细胞外信号调节激酶-2的磷酸化。在电子自旋共振研究中，白藜芦醇减少羟自由基（OH(-)）的形成。在体内研究中，白藜芦醇（5毫克/千克）显著延长小鼠血小板血栓形成时间。总之，本研究的主要发现表明，白藜芦醇的抑制作用可能涉及：（i）抑制p38 MAPK - 胞质磷脂酶A(2) - 花生四烯酸 - TxA(2) - [Ca(+2)]i级联反应；（ii）激活一氧化氮/环磷酸鸟苷，从而抑制磷脂酶C和/或PKC活化。白藜芦醇可能通过抑制血小板聚集在血栓栓塞相关疾病中发挥显著的保护作用。
