PRETREATMENT WITH NEBIVOLOL ATTENUATES LEVEL AND EXPRESSION OF MATRIX METALLOPROTEINASES IN A RAT MODEL OF RENAL ISCHEMIA-REPERFUSION INJURY.

AIM Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a β1-adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. METHODS 20 Wistar albino rats were divided into three groups: sham-operated , ischemia-reperfusion, and nebivolol-pretreated . IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by gelatin zymography and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS Creatinine levels increased significantly in the ischemia-reperfusion group compared to sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. CONCLUSION Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.