Role Of PI3K/Nrf2 Signaling Pathway On Endotoxin-induced Acute Kidney Injury In Rabbits

Objective To evaluate the role of Phosphoinositide 3-kinase/NF-E2 related factor 2 signaling pathway in endotoxin-induced acute kidney injury in rabbits.Methods Fifty healthy male New Zealand white rabbits,aged 2 months, weighing 1.5-2.0 kg,were divided into 5 groups randomly(n=10 each):control group(group C),endotoxin shock group(group L), endotoxin shock +wortmannin group(group WL),wortmannin group(group W),dimthyl sulfoxide(DMSO) group(group D)。Wortmannin 0.6mg/kg was injected via the auricular vein in group W and WL, DMSO 0.08ml/kg was injected via the auricular vein in group D,while normal saline(NS) 0.08ml/kg was injected via the auricular vein in group C and L.30 minutes later,lipopolysaccharide(LPS) 5mg/kg was injected via the auricular vein in group L and WL,while the equal volume of normal saline was injected via the auricular vein in group C,D and W.The rabbits were sacrificed at 6 hours after LPS or normal saline administration.The kidneys were removed for microscopic examination. The pathological changes of the kidney were scored.The concentrations of serum urea nitrogen(BUN) and creatinine(Cr),urinary α1- microglobulin(α1-MG) concentration, MDA content,SOD activity in renal tissue and the expression of Nrf2 mRNA,HO-1 mRNA, p-Akt protein,total Nrf2 protein,nuclear Nrf2 protein and HO-1 protein in renal tissue were detected.Results Compared with group C,D and W,the pathological score,the concentrations of serum BUN and Cr, urinary α1-MG concentration,MDA content and the expression of Nrf2 mRNA,HO-1 mRNA, p-Akt protein,total Nrf2 protein,nuclear Nrf2 protein and HO-1 protein in renal tissue were significantly increased(P<0.05), while SOD activity was significantly decreased in group L and WL(P<0.05). There were no significant changes among group C,W and D(P>0.05). Compared with group L,the pathological score,concentrations of serum BUN and Cr, urinary α1-MG concentration and MDA content were increased significantly(P<0.05),while SOD activity, expression of Nrf2 mRNA, HO-1 mRNA, p-Akt protein,total Nrf2 protein, nuclear Nrf2 protein and HO-1 protein in renal tissue were significantly decreased in group WL(P<0.05).Conclusion Activation of PI3K/Nrf2 singaling pathway maybe one of the regulatory mechanisms of the body adapting to the endotoxin-induced acute kidney injury in rabbits.HO-1 protein maybe one of the protective mechanisms of endotoxin-induced acute kidney injury through the PI3K/Nrf2 signaling pathway.