Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition.

Abstract

The aim of this study was to investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced sepsis and the possible mechanism. Thirty male Sprague-Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham-operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1. The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham-operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1 expression in sepsis + NGAL group were significantly higher than those in the sham-operated group and the sepsis group (P < 0.05). NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO-1.