背景：Lumbrokinase是一個從中藥地龍抽提出的血酸溶解酵素， Lumbrokinase在臨床上已經被應用在中風以及心血管疾病的治療，然而，發炎反應和Lumbrokinase的心臟保護作用的關係仍然未知，在本研究中，我們將研究Lumbrokinase在於大鼠心肌缺血再灌注傷害的心臟保護作用，並評估在於大鼠心肌缺血再灌注傷害所誘發的發炎反應中，Lumbrokinase是否參與發炎反應相關之訊息路徑因子之調節，來達到心臟保護作用。 實驗方法：本研究計畫採用麻醉大鼠左冠狀動脈結紮六十分鐘而後再灌注三小時的心肌缺血再灌注動物模式，藉由觀察心肌缺血再灌注誘發之心律不整以及心肌梗塞體積評估Lumbrokinase在大鼠心肌缺血再灌注傷害的心臟保護作用。 結果：研究發現Lumbrokinase可以減少動物死亡率並且抑制心肌缺血再灌注傷害誘發之心律不整以及心肌梗塞體積，同時Lumbrokinase也可以減少動脈血漿中的LDH。此外，Lumbrokinase可以減少缺血再灌注傷害的心肌的COX-2, iNOS以及MMP-9的蛋白質表現量。 結論：研究發現大鼠左冠狀動脈結紮一小時而後再灌注三小時的傷害下，Lumbrokinase在大鼠心肌缺血再灌注傷害具有心臟保護作用，可以減少動物死亡率，心律不整的發生以及降低心肌梗塞的體積，並發現Lumbrokinase可能是藉由減少缺血再灌注傷害的心肌的COX-2, iNOS以及MMP-9等發炎蛋白質表現量來達到心臟保護作用。
BACKGROUND Lumbrokinase, a novel antithrombotic agent purified from the earthworm Lumbricus rubellus, has been clinically used to treat stroke and cardiovascular diseases. However, inflammatory responses in the cardioprotective effect of lumbrokinase remain unknown. In this study, the cardioprotective effect of lumbrokinase and the signaling pathways involved in lumbrokinase-inhibited expression of inflammation mediators were investigated in rats subjected to myocardial ischemia-reperfusion (I-R) injury. METHODS The left main coronary artery of anesthetized rats was subjected to 60 min occlusion and 3 h reperfusion. The animals were administrated with and without lumbrokinase, and the severity of I-R-induced arrhythmias and infarction were compared. RESULTS Lumbrokinase inhibited I-R-induced arrhythmias and mortality and myocardial infarction. Lumbrokinase decreased the lactate dehydrogenase levels in carotid blood during the same period. Lumbrokinase also inhibited the enhancement of the I-R induced expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-9. CONCLUSIONS These findings suggest that lumbrokinase is a potent antiarrhythmic agent with cardioprotective properties in rats with I-R injury. The cardioprotective effects of lumbrokinase may be correlated with its inhibitory effect on the I-R-induced expression of COX-2, iNOS and MMP-9.
