Effects of sodium selenite on renal function in rats with contrast-induced acute kidney injury and the Nrf2/ARE signaling pathway
Objective To investigate the effects of sodium selenite(SS)on renal function in contrast-induced acute kidney injury(CIAKI)rats and the nuclear factor erythroid-2 related factor 2(Nrf2)/antioxidant responsive element(ARE)signaling pathway.Methods Male Sprague-Dawley(SD)rats in the specific-pathogen free(SPF)grade were randomly grouped into control group,model group,low-dose SS group(0.1mg/kg),medium-dose SS group(0.3mg/kg),high-dose SS group(0.5mg/kg),and inhibitor group(10mg/kg Nrf2/ARE pathway inhibitor all-trans retinoic acid[ATRA]),with 12 rats in each group.Except for rats in the control group,CIAKI modeling was performed in the remaining groups.Three days before and three days after modeling,each group was given corresponding intervention measures.Fully automated biochemical analyzer was used to detect renal function indicators,such as blood urea nitrogen(BUN)and serum creatinine(Scr).Hematoxylin and eosin(H&E)staining was applied to observe pathological changes in renal tissues.Fluorescence probe method was applied to detect reactive oxygen species(ROS)in renal tissues.Relative level of glutathione peroxidase(GSH-Px)was measured using a commercial kit.Immunohistochemical staining was applied to detect the positive expressions of Nrf2 and kidney injury molecule-1(KIM-1).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were applied to detect the mRNA and protein expressions of Kelch like ECH related protein 1(Keap1),heme oxygenase 1(HO-1),and quinone oxidoreductase 1(NQO1),respectively.Results Compared with those of control group,rats in the model group presented severe pathological damages to renal tissues,necrosis and shedding of renal tubular cells,swelling and vacuolar degeneration of renal tubular epithelial cells,inflammatory cell infiltration in renal interstitium,significantly higher BUN,Scr,ROS,renal tubular pathological injury score,positive expression of KIM-1,mRNA and protein expressions of Keap1,and significantly lower GSH-Px,positive expression of nuclear Nrf2,mRNA and protein expressions of HO-1 and NQO1(P＜0.05).Compared with those of model group,SS significantly alleviated pathological damages to renal tissues,swelling and vacuolar degeneration of renal tubular epithelial cells,inflammatory cell infiltration in renal interstitium,reduced BUN,Scr,ROS,renal tubular pathological injury score,positive expression of KIM-1,mRNA and protein expressions of Keapl,and elevated GSH-Px,positive expression of nuclear Nrf2,mRNA and protein expressions of HO-1 and NQO1 in a dose-dependent manner(P＜0.05).Compared with those of high-dose SS group,rats in the inhibitor group had aggravated pathological damages to renal tissues and reversed indicators(P＜0.05).Conclusion SS protects CIAKI in rats by inhibiting oxidative stress response and improving renal function via activating the Nrf2/ARE signaling pathway.
acute kidney injurysodium seleniterenal functionnuclear factor erythroid-2 related factor 2antioxidant responsive element
万方数据
维普
