Protective Effect and Potential Mechanism of Erythropoietin on Intestinal Ischemia-reperfusion Injury / 胃肠病学

ABSTRACT

Background:Inflammation plays an important role in intestinal ischemia-reperfusion injury(IRI),and erythropoietin (EPO)has been reported to have anti-inflammatory activity. Aims:To explore the protective effect of EPO on intestinal IRI and its potential mechanism. Methods:Thirty-two healthy male Sprague-Dawley rats were randomly divided into four groupssham operation group(sham group),IRI group,EPO group and 740Y-P group. Rats in IRI,EPO and 740Y-P groups were injected intraperitoneally with 0. 9% NaCl,EPO and EPO + 740Y-P,respectively,one hour before the establishment of intestinal IRI model by superior mesenteric artery clamping(45 min)-reperfusion. All rats were sacrificed one hour after reperfusion. Histopathological changes of small intestine were observed;expression of proteins in PI3K/ Akt and NF-κB signaling pathways was measured by Western blotting;expression and secretion of inflammatory cytokines, including interleukin-8(IL-8),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein-1(MCP-1)were examined by real-time PCR and ELISA. Results:Compared with sham group,the damage score of small intestine,protein expressions of PI3K,p-Akt and p-NF-κB p65,as well as mRNA expressions and serum levels of IL-8,TNF-α and MCP-1 in IRI group were significantly increased(P < 0. 05). EPO pretreatment could ameliorate the histopathological changes of small intestine in IRI model rats,inhibit PI3K/ Akt and NF-κB signaling activation and down-regulate expression and secretion of inflammatory cytokines. When 740Y-P,a PI3K agonist,was used combinedly,the effect exerted by EPO was diminished. Conclusions:EPO pretreatment can protect against intestinal IRI by inhibiting the activation of PI3K/ Akt/NF-κB signaling and the subsequent inflammatory response.