Protective effects of recombinant human erythropoietin against acute liver injury induced by sepsis in rats / 中华急诊医学杂志

ABSTRACT

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute liver injury.Methods Ninety-six healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into 3 groupsnormal control group (sham group,n =32),CLP model group (sepsis group,n =32) and rHuEPO treatment group (n =32).The rat model of sepsis was established by caecal ligation and puncture.In treatment group,rats were treated with rHuEPO 5000 U/kg administered through caudalis vein after CLP procedure.Continuous observation was carried out until 24 h after modeling.Of each group,8 rats were sacrificed at 2 h,6 h,12 h and 24 h,respectively,and then the liver tissue samples and blood samples were collected.Blood samples were assayed for determining the levels of serum cytokines [tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) by using the enzyme-linked immunoadsorbentassay (ELISA) method.The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected.Histopathological changes of liver tissues were observed under optical and transmission electron microscopy.Results (①)The levels of ALT,AST,TNF-a,iNOS in serum of rats in control group were lower than those in model group and rHuEPO group (P ＜0.01).The levels of TNF-α,IL-6 and iNOS in serum of rats in rHuEPO group were decreased significantly compared with model group (P ＜ 0.01).(②) The optical microscopy and the transmission electron microscopy showed hepatocyte edema,liver focal necrosis,inflammatory cell infiltration in portal area and severe congestion of interlobular veins,hepatocyte karyopyknosis,mitochondrial and endoplasmic reticulum (ER) obviously decreased in sepsis group at 24 h.Hepatic injury was attenuated after employment of rHuEPO.Conclusions Recombinant human erythropoietin can inhibit the levels of ALT,AST,TNF-a,iNOS in serum,thus modifying the inflammatory response and providing protective effects against acute liver injury in the wake of infection.