Recombinant human erythropoietin as a novel agent with pleiotropic effects against sepsis-induced acute kidney injury / 中华肾脏病杂志

ABSTRACT

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute kidney injury (AKI).Methods A total of 260 healthy male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groupsnormal control group,sham group,CLP model group,the large dose rHuEPO (5000 U/kg)group,the middle dose rHuEPO (1000 U/kg) group,and the small dose rHuEPO (500 U/kg) group.The rat models of sepsis were established by CLP.In treatment groups,rats were treated with rHuEPO through caudalis injection after CLP surgery.Each group was divided into 2-,6-,12-,24-,36-hour subgroups with 10 rats.Rats were sacrificed and the tissue samples including kidney and blood samples were collected.The kidney function,plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)],kidney injury moleclue 1 (KIM-1) and inducible nitric oxide synthase (iNOS)were measured.Cytokines were determined by ELISA method.The expression of nuclear factor-kappaB (NF-κB) protein in kidneys were detected by immnunohistochemistry method.Pathological changes of kidney tissues were observed by light and transmission electron microscopy for cytokine content and apoptosis.Results Compared with CLP model group,renal function,the levels of TNF-α,IL-6,KIM-1 and iNOS in serum,the expression of NF-κB,significantly decresed in large dose rHuEPO group (all P ＜ 0.05).rHuEPO also lessened the histological changes in large dose group.rHuEPO did not lessen the histological changes in others.Conclusion rHuEPO can inhibit the levels of TNF-α,IL-6 and iNOS in serum,thus modify the inflammatory response and provide protective effects against acute kidney injury induced by sepsis.