title: Heparin-binding epidermal growth factor-like growth factor is essential for preservation of gut barrier function after hemorrhagic shock and resuscitation in mice.
abstract: BACKGROUND
  The aim of the current study was to determine the role of heparin-binding (HB) epidermal growth factor (EGF)-like growth factor as a mediator of gut barrier function after hemorrhagic shock and resuscitation (HS/R) in mice.
  
  
  METHODS
  HS/R was induced in HB-EGF knockout (KO) and wild-type (WT) mice. Intestinal histologic injury scores, intestinal epithelial cell apoptosis, and gut barrier function were determined. Statistical analyses were performed using linear mixed models with P<.05 considered significant.
  
  
  RESULTS
  All mice subjected to HS/R had significantly increased intestinal histologic injury scores, apoptosis indices, and intestinal permeability compared with mice subjected to sham operation. Compared with WT mice, HB-EGF KO mice subjected to HS/R had significantly increased histologic injury (mean injury grade, 4.5 +/- 1 vs 2.75 +/- 0.5 at 3 hours of resuscitation; P<.05), increased apoptosis indices (mean apoptosis index, 6.84 +/- 1.95 vs 3.24 +/- 1.00 at 3 hours of resuscitation; P < .05), and increased mucosal permeability (FD4 clearance 78 +/- 18.91 vs 47.75 +/- 8.06 nL/min/cm(2) at 3 hours of resuscitation; P<.05).
  
  
  CONCLUSIONS
  HB-EGF is essential for the preservation of gut barrier function after HS/R. These findings support the clinical use of HB-EGF in protection of the intestines from disease states associated with intestinal hypoperfusion injury.
authors.affiliation: Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhang
authors.forename: Andrei
authors.initials: A
authors.lastname: Radulescu
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D017209:Apoptosis; D020895:Enterocytes / Q000473:pathology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins