title: Transduced PEP-1-heme oxygenase-1 fusion protein reduces remote organ injury induced by intestinal ischemia/reperfusion.
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.
  
  
  METHODS
  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.
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Xiang-Hu
authors: XH
authors: He
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Qing-Wen
authors: QW
authors: Li
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Yan-Lin
authors: YL
authors: Wang
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Zong-Ze
authors: ZZ
authors: Zhang
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Jian-Juan
authors: JJ
authors: Ke
authors: Department of Anesthesiology, Shenzhen Boan Maternity and Child Health Hospital, Shenzhen, Guangdong, China (mainland).
authors: Xue-Tao
authors: XT
authors: Yan
authors: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China (mainland).
authors: Kai
authors: K
authors: Chen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; C561500:PEP-1-heme oxygenase-1 fusion protein; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase