The effect of NF-κB on apoptosis of renal tubular cells in acute kidney injury induced by ischemia-reperfusion in mice

Abstract

Objective To observe the effect of signal transduction pathway of NF-κB on tubular cell apoptosis in ischemia-reperfusion induced acute kidney injury (AKI) in mice.Methods Eighteen C57B/6 mice were randomly (random number) divided into three groups,namely control group,AKI group,and pyrrolidine dithiocarbamate (PDTC) group.AKI model of mouse was made by occlusion of bilateral renal pedicles with microvascular clamps for 45 minutes,and intraperitoneal injection of PDTC (50 mg/kg) was given immediately after modeling in mice of PDTC group.Forty-eight hours after modeling,kidney pathological changes,serum creatinine (SCr) and blood urea nitrogen (BUN) were examined,and renal tissue NF-κB,TNFR,Bcl-2 and caspase-3 levels were detected by using immunohistochemistry,and tubular cell apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL).Results (1) The pathological Pallers score of renal damage,blood urea nitrogen and serum creatinine levels in PDTC group were significantly lower than those in AKI group [(2.83 ± 0.41)vs.(4.50± 0.55),P=0.000; (61.65 ±3.06) mmol/L vs.(77.78 ±5.82)mmol/L,P=0.000and (74.33 ± 9.83) μmol/L vs.(152.00 ± 16.55) μmol/L,P =0.000,respectively].(2) The level of NF-κB in renal tissue homogenates in PDTC group was significantly lower than that in AKI group [(20.33± 2.34) ％ vs.(35.83 ± 3.06) ％,P =0.000].(3) The apoptotic index of renal tubular cells in PDTC group was significantly lower than that in AKI group [(16.67 ± 1.15) ％ vs.(28.00 ±2.01) ％,P =0.001].(4) The levels of caspase-3 and TNFR1 in renal tissue homogenates in PDTC group were significantly lower than those in AKI group [(7.00 ± 1.26) vs.(11.00 ± 1.26),P =0.000 and (5.55 ± 0.82) vs.(9.75 ± 0.76),P =0.000],and Bcl-2 level in PDTC group was significantly higher than that in AKI group [(10.50± 1.38)vs.(1.83 ±0.98),P=0.000].Conclusions NF-κB activates renal tubular cell apoptosis in acute kidney injury induced in mice after ischemia-reperfusion.Blockade of NF-κB signal transduction pathway may lessen the apoptosis of renal tubular cells,leading to renal function less compromised. Key words: Acute kidney injury ; NF-κB ; Apoptosis ; Ischemia-reperfusion injury ; Pyrrolidine dithiocarbamate; Tumor necrosis factor receptor-1