Inhibition of cyclooxygenase-2 prevents intra-abdominal adhesions by decreasing activity of peritoneal fibroblasts

Abstract

Guangbing Wei,1 Xin Chen,2 Guanghui Wang,1 Pengbo Jia,1,3 Qinhong Xu,2 Gaofeng Ping,1 Kang Wang,1 Xuqi Li1 1Department of General Surgery, 2Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 3Department of General Surgery, First People’s Hospital of Xianyang City, Xianyang, People’s Republic of China Background: Postoperative intra-abdominal adhesions are common complications after abdominal surgery. The exact molecular mechanisms that are responsible for these complications remain unclear, and there are no effective methods for preventing adhesion formation or reformation. The aim of the study reported here was to investigate the preventive effects and underlying potential molecular mechanisms of selective cyclooxygenase-2 (COX-2) inhibitors in a rodent model of postoperative intra-abdominal adhesions.Materials and methods: The expression of COX-2 in postoperative intra-abdominal adhesions and normal peritoneal tissue was examined by immunohistochemistry and Western blot analysis. Assays were performed to elucidate the effect of COX-2 inhibition on hypoxia-induced fibroblast activity in vitro and on intra-abdominal adhesion formation in vivo.Results: Hypoxia-induced COX-2 expression in peritoneal fibroblasts was increased in postoperative intra-abdominal adhesions. Inhibition of COX-2 attenuated the activating effect of hypoxia on normal peritoneal fibroblasts in vitro. Data indicate that selective COX-2 inhibitor prevents in vivo intra-abdominal adhesion by inhibition of basic fibroblast growth factor and transforming growth factor-beta expression, but not through an antiangiogenic mechanism. Furthermore, using selective COX-2 inhibitors to prevent intra-abdominal adhesions did not adversely affect the weight, bowel motility, or healing of intestinal anastomoses in a rat model.Conclusion: These results show that hypoxia-induced COX-2 expression in peritoneal fibroblasts is involved in the formation of intra-abdominal adhesions. Inhibition of COX-2 prevents postoperative intra-abdominal adhesions through suppression of inflammatory cytokines. Keywords: postoperative adhesions, COX-2, hypoxia, COX-2 inhibitors