Pretreatment with nebivolol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischaemia–reperfusion injury

Abstract

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 ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischaemia-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. Twenty Wistar albino rats were divided into three groups: sham-operated , ischaemia-reperfusion, and nebivolol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45min followed by 24h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. Creatinine levels increased significantly in the ischaemia-reperfusion group compared to the 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. Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.