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Exogenous pulmonary surfactant prevents the development of intra‐abdominal adhesions in rats
Authors:Paulo C Silva  Hugo Macedo‐Ramos  Johnatas D Silva  Pedro A C Teixeira  Vera L N Pannain  Wagner Baetas‐da‐Cruz
Institution:1. Centre for Experimental Surgery, Department of Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2. Translational Laboratory in Molecular Physiology, Centre for Experimental Surgery, Department of Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;3. Postgraduate Program in Biological Sciences – Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;4. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;5. Laboratory of Glycobiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;6. Department of Pathology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;7. Postgraduate Program in Surgical Science, Department of Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Abstract:Intra‐abdominal adhesions are major post‐operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post‐operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L‐S and GE‐S, respectively). Intra‐abdominal adhesions, collagen fibre content, metalloproteinase (MMP)‐9, expression of growth factors (TGF‐β, KGF and VEGF), type III procollagen (PCIII) and pro‐caspase 3, as well as isolectin B4 and ED1‐positive cells expressing MMP‐9, were evaluated. Groups treated with surfactant (GE‐S and L‐S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE‐S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP‐9 expression and activity in the GE‐S group compared to the GE group (P < 0.05). ED1‐positive cell counts were significantly higher in the GE‐S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP‐9+. Double‐labelling of MMP‐9 with IB4 showed no significant differences between GE‐S and GE groups. TGF‐β, KGF, PCIII and pro‐caspase‐3 mRNA expression decreased significantly in GE‐S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE‐S group. These findings suggest that surfactant reduces the intra‐abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra‐abdominal adhesions with surfactant and to endorse its putative mechanism of action.
Keywords:peritoneal adhesions  gastrointestinal surgery  inflammation  matrix metalloproteinase  transforming growth factor‐β    type III procollagen
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