Abstract

Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson’s trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression levels of TGF-β1, fibrinogen and α-SMA protein and mRNA in the rat peritoneum or adhesion tissues were also down-regulated following the combined administration of KGF and HA. The combined administration of KGF and HA can significantly prevent postoperative intra-abdominal adhesion formation by maintaining the separation of the injured peritoneum and promoting mesothelial cell regeneration. The potential mechanism may be associated with rapid mesothelial cell repair in the injured peritoneum. This study suggests that combined administration of KGF and HA may be a promising pharmacotherapeutic strategy for preventing abdominal adhesions, which is worth further study, and has potential value in clinical applications.

Highlights

  • Postoperative intra-abdominal adhesions are a very common complication of abdominal surgery that may occur in 90% to 95% of patients undergoing abdominal surgery [1,2,3]

  • This study investigated whether the combined administration of Keratinocyte growth factor (KGF) and sodium hyaluronate (HA) can prevent intra-abdominal adhesions in rats by promoting the orderly repair of the injured peritoneal mesothelial cell layer

  • The results of this study have shown that, compared to the administration of either KGF or HA alone, the combined administration of KGF and HA can more effectively prevent intra-abdominal adhesion formation in a rat model

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Summary

Introduction

Postoperative intra-abdominal adhesions are a very common complication of abdominal surgery that may occur in 90% to 95% of patients undergoing abdominal surgery [1,2,3]. Fibrin deposition can persist and form permanent fibrous adhesions when fibrinolytic activity is decreased due to poor mesothelial cell regeneration. To this end, mesothelial injury is considered to be one of the causes of peritoneal adhesion formation [9]. KGF has rarely been reported to prevent intra-abdominal adhesions by promoting mesothelial cell regeneration. KGF has been shown to improve mesothelial cell proliferation, which may enhance fibrinolytic activity to potentially suppress postoperative adhesions [13]. This study investigated whether the combined administration of KGF and sodium hyaluronate (HA) can prevent intra-abdominal adhesions in rats by promoting the orderly repair of the injured peritoneal mesothelial cell layer.

Discussion
Agents
Surgical Procedures
Adhesion Grade and Assessment
Picrosirius Red Staining for Collagen
Immunohistochemistry
Western Blot
Real-Time RT-PCR
4.10. Hydroxyproline Determination
Findings
4.11. Statistical Analyses
Full Text
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