Protective Effect And Mechanisms Of Neutrophil Gelatinase-associated Lipocalin On Acute Kidney Injury In Sepsis Rat

Objective:To investigate the protective effect and possible mechanisms of neutrophil gelatinase-associated lipocalin (NGAL) on acute kidney injury in sepsis rat.Methods:We made the sepsis rat model by cecal ligation and puncture(CLP),30Male Sprague-Dawley rats were randomly assigned to three groups. Group A(n=10) was the sham operation group, group B (n=10) with CLP+saline, group C(n=10) with CLP+NGAL. Rat blood were collected before modeling(Oh) and after24h, for serum creatinine (Scr) and blood urea nitrogen (BUN) detecting. All rats were killed after24h, the right renal tissue was taken for pathological section. The pathological change of kidney tissues were investigated using hematoxylin-eosin staining; expression of apoptosis-regulating protein Caaspase-3and Bax were detected using immunohistochemical staining.; the apoptosis of renal tubular epithelial cell was detected using terminal dUTP nick-labeling method. The left kidney tissue were homogenates prepared for detecting malondialdehyde (MDA) and Superoxide Dismutase (SOD) content by enzyme-linked immunosorbent assay (ELISA). Results:Compare with0h,the Scr and BUN at the24h were increased significantly in group B and group C, P<0.05; The Scr and BUN in group B were increased more than group A and group C, P<0.05. In H-E staining, the renal injury in group B was the most serious one, kidney tissues injury in group C was milder than in group B. The results of immunohistochemistry showed that the Caspase-3and Bax protein expression in group A were(0.43±0.25)%and (1.37±1.1)%;group C were (7.32±2.04)%and (12.73±4.18)%, lower than group B (20.33±2.01)%and (49.2±8.55)%,(P<0.05). Kidney tissue TUNEL staining of apoptotic cells in group A was occasionally, in group C13.6±3.42cells/high-power field, was significantly lower than group B26.4±7.2cells/high-power field,(P<0.05). The results in ELISA test showed that:MDA in group A and C were significantly lower than group B (P<0.05);SOD in group C was significantly higher than group B (P<0.05).Conclusion:NGAL could protect against acute kidney injury by inhibitting the activation of Caspase-3, reducing the level of pro-apoptotic protein Bax, reducing apoptosis, inhibitting lipid oxidation, and reducing tissue damage.