Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions.
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.
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. weiguangbing1208@163.com.
Guangbing
G
Wei
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. trytofly@stu.xjtu.edu.cn.
Cancan
C
Zhou
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. amon@mail.xjtu.edu.cn.
Guanghui
G
Wang
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. linnet@mail.xjtu.edu.cn.
Lin
L
Fan
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. wangkang5754@163.com.
Kang
K
Wang
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. lixuqi@163.com.
Xuqi
X
Li
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004848:Epithelium / Q000502:physiology; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology / Q000627:therapeutic use*; D005782:Gels / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011182:Postoperative Care; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D000199:Actins; D024042:Collagen Type I; D005340:Fibrinogen; D051523:Fibroblast Growth Factor 7; D005782:Gels; D006820:Hyaluronic Acid; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat
keratinocyte growth factor; mesothelial cells; peritoneum; postoperative adhesions; regeneration
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