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  • Title: Pretreatment With Erythropoietin Attenuates Intestinal Ischemia Reperfusion Injury by Further Promoting PI3K/Akt Signaling Activation.
    Author: Kai-lan W, Si Z.
    Journal: Transplant Proc; 2015; 47(6):1639-45. PubMed ID: 26293027.
    Abstract:
    BACKGROUND: Erythropoietin (EPO) has been shown to be beneficial in resolution of acute inflammation and intestinal ischemia/reperfusion (IR) injury is featured by the excessive immune response. The current research is designed to evaluate the effect and potential mechanisms of EPO on the intestinal IR injury. Therefore, the effect of EPO on intestinal IR injury was examined by the change of intestinal histology; the expression of pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ); and the protein levels of EPOR, p-EPOR, p85, p-p85, Akt, p-Akt, IκΒ-α, p-p65, and p65. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups: sham group (sham), IR-saline group (IRI), and the IR-EPO group (EPO). Rats were treated with EPO (5000 U/kg) 1 hour before IR induction. A rat model of IR injury was established by ligating the superior mesenteric artery for 30 minutes, followed by reperfusion for 1 hour. Intestinal histology, pro-inflammatory cytokines, and mediators were assessed. The effect of EPO on PI3K/Akt/NF-κB signaling and EPOR were also measured. RESULTS: EPO significantly decreased the pathologic changes of intestinal and reduced the elevation of pro-inflammatory cytokines TNF-α, IL-1β, and IFN-γ in intestinal and serum caused by IR which was associated with suppressing NF-κB activation by further promoting activation of PI3K/Akt signaling. CONCLUSIONS: EPO ameliorated the acute intestinal injury caused by IR, which was associated with further activating PI3K/Akt signaling to suppress NF-κΒ-mediating inflammation. Our findings suggest that EPO could be useful for preventing IR-induced intestinal injury.
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