Transduced PEP-1-heme oxygenase-1 fusion protein reduces remote organ injury induced by intestinal ischemia/reperfusion.
Med Sci Monit
; 21: 1057-65, 2015 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-25863938
ABSTRACT
BACKGROUND:
A 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 ANDMETHODS:
We 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.RESULTS:
Malondialdehyde 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.CONCLUSIONS:
This 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução Genética
/
Proteínas Recombinantes de Fusão
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Traumatismo por Reperfusão
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Heme Oxigenase-1
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Intestinos
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Fígado
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Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article