Mechanisms of Platelet Activation and Antiplatelet Drugs

血小板活化機轉與抑制血小板凝集藥物

施靖瑜(Ching-Yu Shih) ； 周志中(Tz-Chong Chou)

《童綜合醫學雜誌》 4卷1期 (2010/06) Pp. 1-11

https://doi.org/10.29838/TMJ.201006.0001

摘要

血小板最重要的功能為止血，但當血小板活化時也會產生許多前發炎物質及具生物活性的介質，進而促使血塊形成及發炎反應。已經有許多臨床實驗指出血小板過度活化與血栓形成及許多心血管疾病的產生有密切的相關性。因此在臨床上使用抗血小板活化藥物在預防及減緩血栓及發炎反應的發生應有好處。血小板的活化是非常複雜的過程，受到多種不同的訊息路徑及物質所調控，其中花生四烯酸(arachidonic acid)可經由環氧合酶(cyclooxygenase, COX)及thromboxane合成酶催化所生成之thromboxane A2 (TXA2)即是一個很重要的血小板凝集活化劑，另外由phospholipase C所調控產生之inositol 1,4,5-trisphosphate (IP3)及diacylglycerol (DAG)可分別促使鈣離子由血小板dense tubular system釋放及活化protein kinase C活性，最終造成血小板活化。而另一方面cyclic AMP及cyclic GMP則是扮演著負向調控血小板凝集反應的角色，可抑制血小板吸附，顆粒內含物質的釋放，TXA2形成和細胞內鈣離子移動。目前很多針對抑制血小板活化路徑及物質所設計出來的抗血小板凝集藥物在臨床上已廣為使用，這些標靶分子包括血小板膜上ADP P2Y12，integrin IIbβ3接受器，COX1，cyclic AMP及cyclic GMP phosphodiesterase等。在我們先前的研究中也發現了一些臨床藥物和天然物質等具有明顯的抗血小板凝集的作用，例如amlodipine，simvastatin，alpha-lipoic acid，c-phycocyanin及新合成化學藥物等可經由其特定的機轉而達到抑制血小板凝集之作用。

關鍵字

血小板活化 ； 抗血小板凝集藥物

並列摘要

Platelets are essential for primary hemostasis. However, upon activation, platelets also produce several pro-inflammatory and bioactive mediators promoting clot formation and inflammatory responses. A lot of clinical trails have shown that platelet hyperactivity is implicated in the pathogenesis of thrombus formation, and several vascular diseases. Accordingly, antiplatelet therapy may be a beneficial strategy to prevent and reduce the incidence of vascular thrombosis and inflammation. Platelet activation is a result of a complex signal transduction cascade reaction mediated by various constituents. When platelets are activated, the arachidonic acid-derived thromboxane A2 (TXA2) formation through the actions of cyclooxygenase (COX) and thromboxane synthase is an important inducer to activate platelet function. In addition, phospholipase C-mediated inositol 1,4,5-trisphosphate and diacylglycerol production, and subsequently induces calcium release from the dense tubular system and activates protein kinase C respectively, which leads to platelet activation. On the other hand, cyclic AMP and cyclic GMP, endogenous negative regulators of platelet responses, inhibit adhesion, aggregation, release of granule contents, production of TXA2, and intracellular Ca(superscript 2+) mobilization of platelets upon stimulation. Several antiplatelet agents targeting key pathways of platelet activation have been used in clinical therapy. These targets include platelet surface ADP P2Y12, integrin aIIbβ3 receptors, COX1, cyclic AMP, and cyclic GMP phosphodiesterases etc. Furthermore, our previous studies have found that some clinical drugs and natural products such as amlodipine, simvastatin, alpha-lipoic acid, c-phycocyanin and novel synthesized compounds all exert an antiplatelet activity through their specific mechanisms.

並列關鍵字

platelet activation ； antiplatelet drugs