Protective effects of octreotide on renal ischemia-reperfusion injury

Abstract

Objective To investigate the protective effects of octreotide (OCT) on renal ischemia-reperfusion (I/R) injury and its underlying mechanism. Methods Mice were randomly divided into three groups (n=8) using randomized number table method: Sham group, I/R group and octreotide preconditioning (OPC) + I/R group. Mice in group Sham received no treatment of I/R. The renal I/R was established in group I/R and group OPC+ I/R. Serum and renal tissues from these mice were collected 24 h after I/R. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. The renal injury was observed by hematoxylin-eosin (HE) staining. The contents of renal malondialdehyde (MDA)and the activities of superoxide dismutase(SOD)were tested. The levels of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1) and nuclear factor-kappa B (NF-κB) expression in renal tissues were detected by Western blotting. Results The levels of SCr and BUN in I/R group [(113.38±18.39) μmol/L, (32.31±6.66)mmol/L] were significantly higher than in sham group [(27.61±7.77) μmol/L, (11.82±2.56) mmol/L; t=12.153, P=0.000; t=8.124, P=0.000]. The levels of SCr and BUN in OPC+ I/R group [(72.39±11.97) μmol/L, (22.12±3.75) mmol/L] were significantly lower compared to I/R group(t=5.285, P=0.000; t=3.774, P=0.003). Renal tubular injury scores in I/R group (4.13±0.84)were significantly higher than in OPC+ I/R group(2.13±0.64; t=5.736, P=0.000). The MDA levels in I/R group [(5.94±1.23) μmol/g ] were higher than in OPC+ I/R group [(3.92±0.69) μmol/g; t=5.004, P=0.002]. The SOD activities in I/R group [(24.05±6.15) kU/g] were lower than in OPC+ I/R group [(34.64±6.77) kU/g; t=3.276, P=0.006]. The relative expressions of Nrf2 and HO-1 protein in OPC+ I/R group (4.60±0.88, 4.76±0.87) were significantly increased as compared with I/R group (2.35±0.50, 2.67±0.54; t=6.294, P=0.000; t=5.737, P=0.000). The relative expression of NF-κB protein in OPC + I/R group (2.51±0.21) was significantly decreased as compared with I/R group (5.02±0.75; t=7.434, P=0.000). Conclusion OCT protects renal against I/R injury, which may be through activation of Nrf2/HO-1 signaling pathway and downregulation of NF-κB expression. Key words: Octreotide; Renal ischemia; Reperfusion injury; Nuclear factor erythroid 2-related factor 2; Nuclear factor-kappa B