Abstract
BackgroundIntra-abdominal adhesions develop after nearly every abdominal surgery, commonly causing female infertility, chronic pelvic pain, and small bowel obstruction. Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The aim of this study was to investigate whether PTX can reduce post-operative intra-abdominal adhesion formation via collagen deposition, tissue plasminogen activator (tPA) level, inflammation, angiogenesis, and fibrosis.MethodsSeventy male BALB/c mice were randomized into one of three groups: (1) sham group without peritoneal adhesion model; (2) peritoneal adhesion model (PA group); (3) peritoneal adhesion model with PTX (100 mg/kg/day i.p.) administration was started on preoperative day 2 and continued daily (PA + PTX group). On postoperative day 3 and day 7, adhesions were assessed using the Lauder scoring system. Parietal peritoneum was obtained for histological evaluation with hematoxylin and eosin (HE) and picrosirius red staining. Fibrinolysis was analyzed by tPA protein levels in the peritoneum by ELISA. Immunohistological analysis was also conducted using markers for angiogenesis (ki67+/CD31+), inflammation (F4/80+) and fibrosis (FSP-1+ and α-SMA+). All the comparisons were made by comparing the PA group with the PTX treated PA group, and p < 0.05 was considered statistically significant.ResultsIntra-abdominal adhesions were markedly reduced by PTX treatment. Compared with the PA group, PTX treatment had lower adhesion scores than the PA group on both day 3 and day 7 (p < 0.05). Histological evaluations found that PTX treatment reduced collagen deposition and adhesion thickening. ELISA analysis showed that PTX treatment significantly increased the level of tPA in the peritoneum. In addition, in the immunohistological analysis, PTX treatment was found to significantly decrease the number of ki67+/CD31+ cells at the site of adhesion. Finally, we also observed that in the PTX treated group, there was a reduction in the expression of F4/80+, FSP-1+, and α-SMA+ cells at the site of adhesion.ConclusionPTX may decrease intra-abdominal adhesion formation via increasing peritoneal fibrinolytic activity, suppressing angiogenesis, decreasing collagen synthesis, and reducing peritoneal fibrosis. Our findings suggest that PTX can be used to decrease post-operative intra-abdominal adhesion formation.
Highlights
Post-operative intra-abdominal adhesion after laparotomy is a source of considerable morbidity
Seventy BALB/c mice were randomly divided into three different groups: (1) sham group without peritoneal adhesion model; (2) peritoneal adhesion model (PA group, n = 31); (3) peritoneal adhesion model with PTX (Trental) (100 mg/kg/day i.p. once daily) administration was started on preoperative day 2 and continued daily (PA + PTX group, n = 31)
We demonstrated that PTX treatment could effectively reduce post-operative intra-abdominal adhesion formation
Summary
Post-operative intra-abdominal adhesion after laparotomy is a source of considerable morbidity. The pathogenesis of post-operative intra-abdominal adhesion is a complex process that involves inflammation, collagen related clot formation, angiogenesis, fibrinolysis, and tissue repairs which include epithelial-mesenchymal transition (EMT)/endothelial-mesenchymal transition (EndMT) or mesothelial -mesenchymal transition (MMT) (DiZerega, 1997; Hellebrekers & Kooistra, 2011; Homdahl & Ivarsson, 1999). The aim of this study was to investigate whether PTX can reduce post-operative intra-abdominal adhesion formation via collagen deposition, tissue plasminogen activator (tPA) level, inflammation, angiogenesis, and fibrosis. PTX may decrease intra-abdominal adhesion formation via increasing peritoneal fibrinolytic activity, suppressing angiogenesis, decreasing collagen synthesis, and reducing peritoneal fibrosis. Our findings suggest that PTX can be used to decrease post-operative intra-abdominal adhesion formation
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