血小板活化及血小板與白血球共軛是動脈粥狀硬化的重要機轉。心血管疾病多與粥狀動脈硬化有關，其中心肌梗塞更是嚴重的致命性疾病。沒食子酸是紅酒與茶葉當中的主要成分，已被報導具有心血管保護效果。目前認為沒食子酸的心血管保護能力，可能與其抗氧化能力有關。直到最近，沒食子酸對血小板的影響的資料並不多，而且並不一致。因此我們此次的研究目的在於探討沒食子酸對血小板活化的影響及其機轉。我們以健康成年人的血小板作實驗，發現沒食子酸能夠抑制被致效劑刺激的血小板凝集、P-selectin的表現與血小板-白血球共軛，且有劑量效應。胞內鈣離子的增加，是血小板活化的重要步驟，我們的研究發現，沒食子酸能夠抑制血小板胞內鈣離子的釋放。另外，PKCα、MAPK 與 Akt 等訊息傳導，近來也被報導在血小板功能調節上，扮演重要的角色；而 GSK3β 也被證實在血小板的活化抑制上，當作 Akt 的受質 (substrate)。而我們的實驗也證明了。沒食子酸也能夠減少PKCα、p38 MAPK、Akt 與 GSK3β的磷酸化。另外，在我們的血小板實驗當中，沒石子酸對於氧化壓力的抑制效果並不明顯。透過這樣的觀察，我們推測沒食子酸經由抑制 PKCα/p38 MAPK 與 Akt/GSK3β等路徑，同時調節胞內鈣離子的釋放，而達到抑制血小板的功能。這樣的結果是第一次沒食子酸對於血小板功能抑制的機轉探討。另外，我們的研究也提供了動脈硬化性疾病的一個可能治療方向。
Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis, e.g., acute myocardial infarction, remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, had been shown to have properties of cardiovascular protection, which maybe associated with its anti-oxidant effects. Till now, there were scanty data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid can inhibit platelet activation, aggregation and platelet-leukocyte aggregation and to elucidate the possible mechanisms. From our results, gallic acid can dose-dependently inhibit platelet aggregation, P-selectin expression and platelet-leukocyte aggregation. Increase of intracellular Ca2+ is important in platelet activation. We showed that gallic acid prevents intra-cellular Ca2+ release in stimulated platelets. It had been widely studied the activity of PKCα, MAPK and Akt had significant roles in platelet activation. Recently, GSK3βwas recognized as an effector of Akt in regulating platelet function. Our data further disclosed that gallic acid inhibit the phosphorylation of PKCα, MAPK, Akt and GSK3β on platelets stimulated with the agonists (ADP and U46619). Taken together, gallic acid might exert the inhibitory effects on stimulated platelets through attenuating the activity of PKCα/p38MAPK and Akt/GSK3β and preventing the release of intracellular Ca2+. This is the first mechanistic explanation of the platelet inhibitory effects from gallic acid. Our work also provide a possible therapeutic implication in cardiovascular diseases.
