Bianchi Enrica, Boekelheide Kim, Sigman Mark, Lamb Dolores J, Hall Susan J, Hwang Kathleen
Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
J Surg Res. 2016 Mar;201(1):226-34. doi: 10.1016/j.jss.2015.10.044. Epub 2015 Nov 5.
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.
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).
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.
Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model.
腹膜粘连形成是腹部和盆腔手术公认的后果，可导致不孕、慢性盆腔疼痛和肠梗阻。我们推测，胃饥饿素（一种主要存在于胃中的28个氨基酸的肽）在预防术后手术粘连中起重要作用。本研究的目的是建立一种新的手术性腹膜粘连模型，以确定胃饥饿素在伤口愈合和粘连形成中的作用。
C57BL/6野生型小鼠（n = 40）和生长激素促分泌素受体基因敲除（GHSR KO）小鼠（n = 20）接受中线剖腹术，以建立一种腹膜粘连模型，其特征在于两种不同技术的结合：缺血性腹膜纽扣和盲肠多处擦伤。所有小鼠在术后20天每天接受两次腹腔注射胃饥饿素（0.16 mg/kg）或生理盐水。收集腹膜缺血纽扣以确定胶原蛋白的蛋白表达（Masson三色染色、天狼星红染色和蛋白质印迹法）。
该新型小鼠模型显示出一致且易于重现的腹腔内粘连形成。给予胃饥饿素可显著减少野生型小鼠术后粘连形成（P < 0.001）。通过蛋白质印迹分析测量I型胶原蛋白水平，证实了胃饥饿素在野生型小鼠中的抗纤维化作用。在GHSR KO小鼠中未检测到野生型小鼠中所见的胃饥饿素的抗粘连作用，表明这种作用是由GHSR-1a受体介导的。
在小鼠模型中，给予胃饥饿素可能通过减少腹膜粘连形成和纤维化反应来改善手术结果。
