Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Reduces Remote Organ Injury Induced by Intestinal Ischemia/Reperfusion

Abstract

BackgroundA fusion protein composed of heme oxygenase-1 (HO-1) and cell-penetrating peptide PEP-1 has been shown to reduce local intestinal injury after intestinal ischemia/reperfusion (I/R). In this study, we investigated the effects of PEP-1-HO-1 fusion protein on remote organ injury induced by intestinal I/R in rats.Material/methodsWe randomly assigned 24 male Sprague-Dawley rats to 3 groups: Sham, I/R, and I/R plus PEP-1-HO-1 treatment (HO). The model of intestinal I/R was established by occluding the superior mesenteric artery for 45 min followed by 120-min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, while animals in the Sham and I/R groups received the equal volume of physiological saline. At the end of the experiment, lung, liver, and blood samples were collected and analyzed.ResultsMalondialdehyde levels and histological injury scores were increased, and superoxide dismutase activities were decreased in the lung and liver tissues in the I/R group compared with the Sham group (P<0.05). Serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-6, and lung tissue wet weight to dry weight ratio were increased in the I/R group compared with the Sham group (P<0.05). NF-κB expression in intestinal tissues was significantly higher in the I/R group than in the Sham group. These changes were significantly reversed by treatment with PEP-1-HO-1.ConclusionsThis study demonstrates that administration of PEP-1-HO-1 has a protective role against lung and liver injury after intestinal I/R, attributable to the reduction of released proinflammatory cytokines regulated by NF-κB.