Protective effects of recombinant human erythropoietin on acute lung injury induced by sepsis in rats

Abstract

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods Fourty-five rats were randomly (random number) assigned to three groups,namely control group,model group,and rHuEPO group.ALI was induced by intravenous injection of LPS (6 mg/kg).The rHuEPO (5000 U/kg) was injected intravenously into rats 60 min before LPS challenge.The general status of rats was observed.Twelve hours after modeling,the rats were sacrificed and the tissue samples including lung tissue and blood were collected.PaO2,PaCO2,pH,the lung wet/dry weight ratio,plasma cytokines [interleukin (IL) IL-6 and tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) were detected.Cytokines were assayed with ELISA method.Pathological changes of lung tissues were observed under light microscope and transmission electron microscopy.Results (1) Compared with the control group,PaO2,pH in the model group and in the rHuEPO group were significantly lower (P ＜ 0.05),and PaCO2 were significantly higher (P ＜ 0.05).Compared with the model group,PaO2,pH in the rHuEPO group were significantly higher (P ＜ 0.05),and PaCO2 were significantly lower (P ＜ 0.05).(2) Compared with the control group,the W/D weight ratio of lung tissues in the model group and the rHuEPO group was significantly higher (P ＜ 0.05).Compared with the model group,the W/D weight ratio of lung tissues in the rHuEPO group significantly lower (P ＜ 0.05).(3) The levels of TNF-o,IL-6 and iNOS in serum of rats in the control group were lower than those in the model group and the rHuEPO group (P ＜0.01).The serum levels of TNF-α,IL-6 and iNOS of rats in the rHuEPO group were significantly lower compared with the model group (P ＜ 0.01).(4) The light microscopy and the transmission electron microscopy showed the model group had histopathologic changes with acute diffuse lung injury manifested by intra-alveolar hemorrhage,exudate,inflammatory cells infiltration,Ⅰ type and Ⅱ type epithelial cell necrosis and detachment,and the pathological changes of lung tissue in the rHuEPO group were not as serious as those in the LPS group,showing only a little inflammatory cells infiltration of focal alveoli.Conclusions Recombinant human erythropoietin can inhibit the genesis of TNF-α,IL-6 and iNOS in serum,modifying the inflammatory response and providing protective effects against acute lung injury induced by sepsis. Key words: Recombinant human erythropoietin ; Lipopolysaccharides ; Sepsis ; Acute lung injury