title: Ghrelin ameliorates adhesions in a postsurgical mouse model.
abstract: BACKGROUND
  Peritoneal adhesion formation is a well-recognized consequence of abdominal and pelvic surgery, causing infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, a 28-amino acid peptide predominantly found in the stomach, plays an important role in preventing postoperative surgical adhesions. The purpose of this study was to develop a new surgical peritoneal adhesion model to define the role that ghrelin plays in wound healing and adhesion formation.
  
  
  METHODS
  C57BL/6 wild-type mice (n = 40) and growth hormone secretagogue receptor-knockout (GHSR KO) mice (n = 20) underwent a midline laparotomy to establish a peritoneal adhesion model characterized by the combination of two different techniques: ischemic peritoneal buttons and cecal multiple abrasion. All mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 d after surgery. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson trichrome, picrosirius red stain, and Western blot).
  
  
  RESULTS
  The novel mouse model demonstrated consistent and easily reproducible formation of intra-abdominal adhesions. Ghrelin administration significantly reduced postoperative adhesion formation (P < 0.001) in wild-type mice. The antifibrotic effect of ghrelin in wild-type mice was confirmed by measuring collagen I protein levels via Western blot analysis. The anti-adhesion effect of ghrelin seen in wild-type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor.
  
  
  CONCLUSIONS
  Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model.
authors: Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors: Enrica
authors: E
authors: Bianchi
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors: Kim
authors: K
authors: Boekelheide
authors: Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors: Mark
authors: M
authors: Sigman
authors: Department of Urology, Baylor College of Medicine, Houston, Texas.
authors: Dolores J
authors: DJ
authors: Lamb
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors: Susan J
authors: SJ
authors: Hall
authors: Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island. Electronic address: Kathleen_Hwang@brown.edu.
authors: Kathleen
authors: K
authors: Hwang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D054439:Ghrelin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics*; D000267:Tissue Adhesions / Q000517:prevention & control*
chemical_list: D024042:Collagen Type I; D054439:Ghrelin; D054440:Receptors, Ghrelin
keywords: Collagen I; Fibrosis; GHSR-1a receptor; Ghrelin; Postoperative adhesion