Protective effect of vascular endothelial growth factor against cardiopulmonary bypass-associated acute kidney injury in beagles.

The present study aimed to examine the hypothesis that vascular endothelial growth factor (VEGF) has a protective effect against cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI). Eighteen male beagles were randomly allocated to three groups (n=6 per group): Sham group, animals received sternotomy without going through CPB; CPB group, animals received CPB only; VEGF group, animals received CPB and VEGF. VEGF infusion was completed 1 h prior to the initiation of CPB. Renal microcirculation perfusion, serum creatinine (SCr) and blood urea nitrogen (BUN), histopathological injury score and apoptotic index were determined. Hypoxia inducible factor-1 alpha, VEGF, phosphorylated (p)-Akt serine/threonine kinase (Akt), p-endothelial nitric oxide synthase (eNOS), cleaved caspase-3, B-cell lymphoma 2 (Bcl-2) and cluster of differentiation (CD) 95 expression levels were assessed by western blot analysis, Enzyme-linked immunosorbent assay quantitative assays were used to evaluate tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, superoxide dismutase and malondialdehyde levels. Renal microcirculation perfusion of the VEGF group was higher than that of the CPB group (P<0.05) and lower than that of the sham surgery group (P<0.05). SCr and BUN were significantly elevated after CPB in the CPB and VEGF groups, with significantly lower levels in group VEGF than group CPB. Renal pathology scores and apoptotic indices were significantly lower in the VEGF group than the CPB group. Levels of TNF-alpha, IL-6 in the VEGF group were significantly lower than in the CPB group. Levels of VEGF, p-Akt, p-eNOS and Bcl-2 expression in the VEGF group increased significantly in comparison with group CPB. Cleaved caspase-3 in the VEGF group was significantly lower than in the group CPB. CPB-associated reduction of renal microcirculation perfusion may predispose to AKI. VEGF appears to provide a protective effect on the kidneys through improvement in renal microperfusion.