Abstract

Prevention and therapy of thrombotic diseases have attracted much attention in developed countries during recent years. Investigators have been looking for cheaper and safer thrombolytic agents for therapy of thrombotic diseases. Recently, we have discovered a fibrinolytic protease from Schizophyllum commune. In this study, the protease was proven to degrade blood clot effectively. Seven divalent metal ions were used to test the selectiveness on enhancing protease activity. The treated rat blood was traced by thromboelastography to assess the viscoelastic properties of whole blood. As the result, fibrinolytic activity of the protease was enhanced remarkably by Mg2+ in reducing the strength of blood clot and showed the innovative anti-thrombotic effects. This is the first study of anti-thrombotic effects from fungal-derived fibrinolytic protease using thromboelastography and delineates the efficacy of magnesium supplementation in enhancement of thrombolytic activity from S. commune fibrinolytic protease.

中文摘要

近年來，已發展國家中的人們對於預防以及治療血栓性疾病，皆投注以相當高的關注，而同時，科學家們也希望由研究中，可再找到更經濟與安全性更高的抗血栓藥物，來治療血栓性疾病。由本實驗室先前的研究發現，自菇蕈類-裂褶菌 (Schizophyllum commune)醱酵培養物中，有一個具備溶解纖維蛋白活性的活性蛋白酶 (fibrinolytic protease)；於本篇研究中，此溶纖蛋白酶再被證明其具有效溶解血液凝塊的作用；並且，由實驗篩選出對此溶纖蛋白酶活性，具有刺激效果的二價金屬離子，進一步使用溶纖蛋白酶與二價金屬離子共同之處理，觀察其對大鼠血液血栓彈力圖譜 (thromboelastography, TEG)之影響，研究血液凝固作用的進行，與當中各項參數變化。由結果發現，鎂離子具有最明顯提升溶纖蛋白酶活性，且於大鼠血液血栓彈力圖譜分析，鎂離子與溶纖蛋白酶的添加亦顯著地降低血液凝固強度 (clotting strength)，而無抑制血液凝固發生與進行速度之影響。因此，總結以上結果，鎂離子提升作用具有提高溶纖蛋白酶抗血栓形成的有利影響性；而此，本篇文章為首度以血液血栓彈力圖譜分析，觀察真菌溶纖蛋白酶對抗血栓形成影響的研究，並且也指出鎂離子對於提昇裂褶菌溶纖蛋白酶抗血栓活性的有效性。

Keyword: Fibrinolytic protease, Schizophyllum commune, Magnesium, Anti-thrombotic, Thromboelastography.