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HB-EGF protects the lungs after intestinal ischemia/reperfusion injury.

AbstractBACKGROUND:
Acute respiratory distress syndrome continues to be a major source of morbidity and mortality in critically-ill patients. Heparin binding EGF-like growth factor (HB-EGF) is a biologically active protein that acts as an intestinal cytoprotective agent. We have previously demonstrated that HB-EGF protects the intestines from injury in several different animal models of intestinal injury. In the current study, we investigated the ability of HB-EGF to protect the lungs from remote organ injury after intestinal ischemia/reperfusion (I/R).
METHODS:
Mice were randomly assigned to one of the following groups: (1) sham-operated; (2) sham+HB-EGF (1200 microg/kg in 0.6 mL administered by intra-luminal injection at the jejuno-ileal junction immediately after identification of the superior mesenteric artery); (3) superior mesenteric artery occlusion for 45 min followed by reperfusion for 6 h (I/R); or (4) I/R+HB-EGF (1200 microg/kg in 0.6 mL) administered 15 min after vascular occlusion. The severity of acute lung injury was determined by histology, morphometric analysis and invasive pulmonary function testing. Animal survival was evaluated using Kaplan-Meier analysis.
RESULTS:
Mice subjected to intestinal I/R injury showed histologic and functional evidence of acute lung injury and decreased survival compared with sham-operated animals. Compared with mice treated with HB-EGF (I/R+HB-EGF), the I/R group had more severe acute lung injury, and decreased survival.
CONCLUSION:
Our results demonstrate that HB-EGF reduces the severity of acute lung injury after intestinal I/R in mice. These data demonstrate that HB-EGF may be a potential novel systemic anti-inflammatory agent for the prevention of the systemic inflammatory response syndrome (SIRS) after intestinal injury.
AuthorsIyore A O James, Chun-Liang Chen, Guangcun Huang, Hong-Yi Zhang, Markus Velten, Gail E Besner
JournalThe Journal of surgical research (J Surg Res) Vol. 163 Issue 1 Pg. 86-95 (Sep 2010) ISSN: 1095-8673 [Electronic] United States
PMID20599214 (Publication Type: Journal Article)
CopyrightCopyright 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-akt
Topics
  • Animals
  • Apoptosis (drug effects)
  • Capillary Permeability (drug effects)
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins (pharmacology, therapeutic use)
  • Intestine, Small (blood supply)
  • Lung (blood supply, drug effects)
  • Lung Injury (etiology, metabolism, prevention & control)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration (drug effects)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Pulmonary Diffusing Capacity (drug effects)
  • Reperfusion Injury (complications)
  • Respiratory Function Tests

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