N-acetylcysteine attenuated sepsis-induced cardiac depression: down-regulation of MMP-2 pathway in mice

Abstract

During sepsis,the inflammatory responses mediate myocardium injury,including LV dysfunction and cardiac pathophysiological changes. To understanding the pathway of sepsis in cardiac depression,we tested the hypothesis that N-acetylcysteine attenuated sepsis-induced cardiac depression through down-regulation of MMP-2 pathway. Adult (4 to 6 months) male Albino-Webster mice,and their weights ranged from 25 to 30 gm,were pre-treated with N-acetylcysteine ip following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a micro-catheter system. MCP-1 and cytokines mediator’s in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Further,the cardiac MMP2 measured by qRT-PCR and the pathological changes and cells injuries in the myocardium were examined using hematoxylin and eosin staining. CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cTn-I and MMP2. Neutralization of sepsis by NAC resulted in improved LV function and greater reductions in inflammatory mediators,MMP2 and myocardium injury. Taken together,NAC improved LV function following sepsis through down-regulation of MMP2 and serve as a potential therapeutic in cardiac endotoxemia.