Effect of recombinant human erythropoietin on expressions of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 in rats after acute cerebral ischemia

Abstract

Objective To study the influence of recombinant human erythropoietin (rHEPO) in expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in rats after acute cerebral ischemia, explore the anti-oxidant mechanism of rhEPO. Methods Thirty-six healthy male SD rats were randomly divided into sham-operated group,model group,rhEPO treatment group.The rat models of left middle cerebral artery occlusion in the later 2 groups were induced by suture method.rhEPO (5000 IU/kg) was injected intraperitoneally into the rats ofrhEPO treatment group 2 hafter the success of ischemia model making, while those of the sham-operated group and model groupwere given equal volume of saline.Rats were sacrificed 24 h after ischemia; and the levels of Nrf2 andHO-1 in the brain tissues were detected by immunohistochemistry and Western blotting. Results The immunohistochemistry showed that,as compared with those in the sham-operated group,the Nrf2- and HO-1- positive cells obviously increased in rats of the model group and rhEPO treatment group (P＜0.05),and rats of the rhEPO treatment group had significantly larger numbers of Nrf2- and HO-1- positive cells than rats of the model group (P＜0.05); these positive cells were mainly neurons and astrocytes located in ischemic areas.Western blotting also indicated that the expressions of Nrf2 and HO-1 were enhanced in the order of sham-operated group, model group and rhEPO treatment group; statistically significant difference was noted between each 2 groups (P＜0.05). Conclusion The rhEPO may exert a neuroprotective effect by activating Keap1-Nrf2/ARE pathway after acute cerebral ischemia. Key words: Cerebral ischemia; Recombinant human erythropoietin; Nuclear factor erythroid 2-related factor 2; Heme oxygenase-1; Keap1-Nrf2/ARE anti-oxidation system