Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

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.

Preperitoneal Fat Grafting Inhibits the Formation of Intra-abdominal Adhesions in Mice

“…Although various novel strategies have been investigated for treatment of adhesions, 5,17 the optimal solution remains uncovered. When comparing treatment strategies, fat grafting has several advantages: it appears anti-inflammatory and antifibrotic and provides tissue-resident repairing or resolving macrophages to the damaged area.…”

“…3 Mesothelial injury is considered to be one of the causes of peritoneal adhesion formation as the integrity of the mesothelial layer promotes fibrinolytic activity. 4,5 Free fat grafts and processed components of fat are used for reconstruction of soft tissue defects especially in the facial and thoracic region. Novel experimental therapies include softening and contouring of scars and other fibrotic conditions, e.g.…”

Preventive Effects of the Intestine Function Recovery Decoction, a Traditional Chinese Medicine, on Postoperative Intra‐Abdominal Adhesion Formation in a Rat Model

“…Several barrier materials have been used clinically, including hyaluronic acid, carboxymethyl chitin, and oxidized regenerated cellulose, to prevent adhesion by separating the wounded tissues and promoting the repair of mesothelium cells [17–19]. Furthermore, researchers have attempted to prevent postoperative adhesion by inhibiting the inflammatory response [20], regulating fibrinolysis [21], and using antiangiogenesis [22] and antifibrosis [23] methods.…”

TMIGD1 is Expressed at Low Levels in Abdominal Adhesion Tissue and Reduces Oxidative Stress in Peritoneal Mesothelial Cells

“…Mesothelial cell repair plays an extremely important role in the process of adhesion formation [6] . High levels of reactive oxygen species (ROS) are induced in the injured tissue under hypoxic conditions, which can induce higher expression of HIF-1α and activate the TGF/Smad pathway [7] .…”