| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 102 === Lumbrokinase, an antithrombotic agent, extracted from Lumbricus rubellus, has been used to prevent and treat stroke and cardiovascular diseases in clinical. It has been reported that lumbrokinase has some pharmacological properties, including anti-inflammatory, antioxidant, anti-thrombotic and anti-apoptotic. These biological activities might protect heart against myocardial ischemia/reperfusion (I/R) injury. However there is no research reported about whether lumbrokinaset is capable of cardioprotective effect against myocardial I/R injury. This study aim to investigate whether lumbrokinase is capable of cardioprotective effect against myocardial I/R injury in rats and its potential pharmacological mechanisms.
Myocardial I/R injury were established by 60 minutes occlusion of the left anterior descending (LAD) coronary artery and followed by three hours reperfusion in anesthetized male Sprague-Dawley rats. Lumbokinase was administered intravenously 15 minutes before LAD occlusion. We found that lumbrokinase (10 μg/kg) significantly decreased myocardial infarct size, lactate dehydrogenase (LDH) activity, and also significantly reduced the incidence of arrhythmia and mortality than the vehicle group. These results demonstrated that lumbrokinase protected the heart against myocardial I/R injury. To further, we found that toll-like receptor (TLR)-4, phosphorylation- c-Jun N-terminal kinase (p-JNK), phosphorylation-nuclear factor kappa-light-chain-enhancer of B cell (p-NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 expression and metalloproteinase (MMP)-9 activity were significantly increased during myocardial I/R injury. However, lumbrokinase not only significantly attenuated the increased of I/R-induced the expression of TLR4, p-JNK, p-NF-κB, iNOS and COX-2, but also significantly decreased the increased of I/R-induced the activity of MMP-9. Moreover, the results demonstrated that myocardial I/R injury could increased the expression of TLR4 and cause the inflammatory cell infiltration by histopathological stain. And lumbrokinase decreased the expression of TLR4 and the phenomenon of inflammatory cell infiltration in the heart from rats subjected to myocardial I/R injury. Therefore, this study suggested that lumbrokinase was a potential cardioprotective agent to against myocardial I/R injury, and lumbrokinase could against myocardial I/R injury via TLR4/NF-κB/MMP-9 and JNK MAPK signaling pathway.
|
|---|
