Ghrelin ameliorates adhesions in a postsurgical mouse model.

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.

MATERIALS AND 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.