Bo Li1, Ryuta Saka1, Yuichi Takama1, Takehisa Ueno1, Yuko Tazuke1, Hiroomi Okuyama2. 1. Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 2. Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. okuyama@pedsurg.med.osaka-u.ac.jp.
Abstract
PURPOSE: Necrotizing enterocolitis (NEC) remains the leading cause of death in preterm infants. Recombinant human soluble thrombomodulin (rTM) has been reported to have anti-inflammatory effects as well as antithrombogenic effects. The aim of this study was to evaluate the effect of rTM in a rat NEC model. METHODS: NEC was induced by enteral feeding with hyperosmolar formula, gavage administration of lipopolysaccharide and asphyxia stress. Controls were fed by their mother ad libitum. In the treatment group, rTM was administered subcutaneously twice (once each on the first and second day). All animals surviving beyond 96 h or that developed signs of distress were euthanized. The ileum was harvested for a histological evaluation and the measurement of the mRNA and protein expression. RESULTS: The rate of NEC-like intestinal injury in the treatment group (9/25, 36%) was significantly lower than in the NEC group (25/34, 73.5%). Tissue levels of TNF-α, IL-6 and HMGB1 were significantly elevated in the NEC group, whereas those in the treatment group were decreased to similar values as in the control group. CONCLUSIONS: Our experimental study showed that rTM is able to reduce the severity and incidence of NEC. It may be an alternative option for the treatment of NEC.
PURPOSE:Necrotizing enterocolitis (NEC) remains the leading cause of death in preterm infants. Recombinant human soluble thrombomodulin (rTM) has been reported to have anti-inflammatory effects as well as antithrombogenic effects. The aim of this study was to evaluate the effect of rTM in a rat NEC model. METHODS: NEC was induced by enteral feeding with hyperosmolar formula, gavage administration of lipopolysaccharide and asphyxia stress. Controls were fed by their mother ad libitum. In the treatment group, rTM was administered subcutaneously twice (once each on the first and second day). All animals surviving beyond 96 h or that developed signs of distress were euthanized. The ileum was harvested for a histological evaluation and the measurement of the mRNA and protein expression. RESULTS: The rate of NEC-like intestinal injury in the treatment group (9/25, 36%) was significantly lower than in the NEC group (25/34, 73.5%). Tissue levels of TNF-α, IL-6 and HMGB1 were significantly elevated in the NEC group, whereas those in the treatment group were decreased to similar values as in the control group. CONCLUSIONS: Our experimental study showed that rTM is able to reduce the severity and incidence of NEC. It may be an alternative option for the treatment of NEC.
Entities:
Keywords:
Cytokines; Inflammatory; Necrotizing enterocolitis; Rat; Recombinant human soluble thrombomodulin
Authors: Rebecca Maria Rentea; Scott R Welak; Katherine Fredrich; Deborah Donohoe; Kirkwood A Pritchard; Keith T Oldham; David M Gourlay; Jennifer L Liedel Journal: Eur J Pediatr Surg Date: 2012-11-19 Impact factor: 2.191
Authors: Cynthia D Downard; Stephanie N Grant; Paul J Matheson; Alia W Guillaume; Robert Debski; Mary E Fallat; Richard N Garrison Journal: J Pediatr Surg Date: 2011-06 Impact factor: 2.545