- 學位論文
利用血小板功能分析儀及螢光鈉素引起小鼠腸繫膜血管形成血栓之模式評估藥物抑制血栓的活性
study of the anti-thrombotic activity of drugs by two models: platelet function analyzer and flurorescein sodium-induced mesenteric thrombotic formation in mice
摘要
在人體組織受傷時，為維持系統的恆定，避免血液流失，會活化血小板，啟動凝血機制，形成血栓，以達到止血的功用。待受傷的組織修復後，再透過thrombolysis降解。Thrombolysis若未達到其效果，血栓阻塞於血管中，影響血流血量，造成組織受到傷害。而血栓可分為動脈血栓及靜脈血栓，其形成機制不同，靜脈血栓主要是由於血液滯留淤積所造成，而動脈血栓是由於血小板過度活化導致產生血塊堵塞血管，本研究中所使用之藥物多針對動脈血栓治療為方向，針對血小板抗凝集以達到治療血栓的功用。 本篇研究中所測試之五種藥物，於先前的研究中分別證實具有抑制血小板凝集的效果，而本文欲進一步測試這五種藥物in vivo及ex vivo是否亦有抗血栓之效果。 在本研究中測試藥物有：nobiletin ，CME-1，tryphostin AG490；另外還有在中醫上常用於緩解心血管疾病之中藥複方：三黃瀉心湯以及桃仁承氣湯。本實驗室過去已驗證這五種藥對於血小板有抗凝集的作用，在本研究中進一步以兩種實驗模式：一、利用汞燈照射螢光鈉素(fluorescine sodium)所產生的能量刺激內皮細胞誘發在小鼠腸繫膜微血管形成血栓，觀察各藥物抗血栓的情形；二、利用PFA-100R血小板功能分析儀分析各藥物在模擬的微環境下對健康捐贈者的血液血小板凝集功能的影響。在小鼠腸繫膜模式實驗下，可得知這五種藥物皆呈濃度相關性的延緩血栓形成時間。而在PFA-100R 偵測下，這五種藥物亦能延長血小板凝集時間，雖其統計結果未皆達顯著差異，但亦有延長CT(closure time)的傾向。 未來可嘗試再針對各藥物性質之不同作探討，找出更具有療效之抗血栓藥物；亦更廣泛活用這兩種實驗模式，尋找更多具有潛能之抗血栓物質，以利臨床研究上治療及防治血栓的突破。
並列摘要
When blood vessels damage, in order to maintain the homeostasis of the circulatory system, it will active platelet and produce the blood clot. When the damage is repaired, the blood clot will resolve through thrombolysis. If thrombolysis didn’t work out, the blood clot will obstruct the blood vessel and cause the thrombosis. According to the position, it can divide into two types of thrombosis：arterial thrombus and vein thrombus. The mechanism of these two thrombus are not the same. Vein thrombus caused by the stasis of the blood and the arterial thrombus is caused by hyperactivity of platelet. And the drugs used in this study are focused on arterial thrombus. The test drugs in this study：nobiletin(exist in Citrus genus), CME-1(abstract from Cordyceps sinensis), and Tryphosin AG490(JAK2 inhibitor). And the Chinese medicine which could relief the symptoms of cardiovascular : tao-ren-cheng-qi tang(anti-coagulation, dilation of blood vessels and anti-inflammation) and san-hunng xie-xin-tang(lower the blood pressure and anti-coagulation). These drugs already proofed their effect in platelet anti-aggregation. So the further research is to proof their effect in anti-thrombosis in vivo：Use the fluoresin sodium induced thrombosis in mesenteric of mice；and use the PFA-100R to analyze the effect of these drugs in human blood. In vivo model, these five drugs all showed the significantly dose-dependent results. Although ex vivo results not all showed the significantly dose-dependent results, still had it tendency. The next step we hope that we could focus on the different characters of individual drug and find out the most effect drug of anti-thrombosis for the clinical treatment and the breakthrough of anti-thrombosis.
參考文獻
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