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學校名稱輔仁大學
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研究生(中)楊宗餘
研究生(英)Zong-Yu Yang
論文名稱(中)探討牛蒡子苷元抑制血小板凝集之作用機制
論文名稱(英)The Study of Inhibitory Mechanisms of Arctigenin on Platelet Aggregation
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指導教授(中)郭育綺 蔡維人
指導教授(英)Yuh-Chi Kuo Wei-Jern Tsai
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關鍵字(中)牛蒡子苷元
關鍵字(英)Arctigenin
摘要(中)血小板在體內恆定以及凝血機制上面扮演著重要的角色。然而,過度活化的血小板在各種不同的病理上也是主要的成因。PAF 與 TXA2 能透過活化不同的 G 蛋白偶合受體誘發血小板活化凝集。而存在於牛蒡子 ( Bardanae fructus )、水母雪蓮 ( Saussurea medusa )、牛蒡 ( Arctium lappa L. )、日本榧樹 ( Torreya nucifera ) 與槭葉牽牛 ( Ipomea cairica ) 這些植物中的牛蒡子?元,屬於 dibenzylbutyrolactone lignans 的一員,這類物質本身兼具有抗氧化及抗發炎的功效。根據文獻報導,牛蒡子?元為 PAF 受體的拮抗劑 ( antagonist )。本實驗首次以血小板為材料,發現 arctigenin 能有效抑制 PAF 所媒介的紐西蘭大白兔血小板凝集及細胞內鈣離子移動。此外arctigenin亦可抑制 AA 與 U46619 對血小板引發的凝集,其對 AA 之抑制作用,可能是透過部份影響 AA 的代謝:另一方面,arctigenin 可分別抑制鈣離子的移動與 PMA 活化之血小板凝集,故推測可能經由協同作用,而降低 U46619 所誘發的血小板凝集。
摘要(英)Platelets play essential roles in the hemostasis and thrombosis. However, overactivition of platelet would become an important factor in a wide range of pathological conditions. Platelet-activating factor ( PAF ) and thromboxane A2 ( TXA2 ) activate multiple G protein-mediated signaling pathways and result in platelet aggregation. Arctigenin, naturally exiting in Bardanae fructus, Saussurea medusa, Arctium lappa, Torreya nucifera, and Ipomea cairica, is a phenylpropanoid dibenzylbutyrolactone lignan with antioxidant and anti-inflammatory activities. Previous study reported arctigenin was a PAF antagonist. The present study demonstrated for the first time that pretreatment of arctigenin could inhibit PAF-mediated rabbit platelet aggregation and calcium mobilization. Moreover, arctigenin could suppress platelet aggregation stimulated by AA and U46619. The inhibition of AA-induced platelet aggregation by arctigenin might be partialy correlated with AA metabolism. On the other hand, arctigenin synergistically reduced platelet activaty might result form the decrease of calcium mobilization and PMA-evoked platelet aggregation.
論文目次壹、縮寫表----------------------------------------------------------------------------- 1 貳、中文摘要-------------------------------------------------------------------------- 3 英文摘要-------------------------------------------------------------------------- 4 參、序論-------------------------------------------------------------------------------- 5 一、止血反應與血栓形成----------------------------------------------------- 5 二、血小板結構----------------------------------------------------------------- 8 三、血小板的活化反應------------------------------------------------------- 11 四、訊息傳導------------------------------------------------------------------- 14 五、牛蒡子?元---------------------------------------------------------------- 22 肆、實驗動機與目的---------------------------------------------------------------- 24 伍、實驗材料與方法---------------------------------------------------------------- 27 一、血小板懸浮液之製配---------------------------------------------------- 27 二、血小板凝集測試---------------------------------------------------------- 28 三、乳酸脫氫?活性測試---------------------------------------------------- 28 四、丙二醛之測定------------------------------------------------------------- 29 五、細胞內鈣離子移動測試------------------------------------------------- 29 六、實驗數據統計分析------------------------------------------------------- 30 陸、實驗結果------------------------------------------------------------------------- 31 柒、討論------------------------------------------------------------------------------- 37 捌、參考資料------------------------------------------------------------------------- 42 玖、表---------------------------------------------------------------------------------- 56 拾、圖---------------------------------------------------------------------------------- 57
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