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Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model

  • Bo Li
  • Ryuta Saka
  • Yuichi Takama
  • Takehisa Ueno
  • Yuko Tazuke
  • Hiroomi OkuyamaEmail author
Original Article

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.

Keywords

Necrotizing enterocolitis Rat Cytokines Inflammatory Recombinant human soluble thrombomodulin 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest in association with this study.

Supplementary material

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Supplementary material 1 (TIFF 8209 kb)
595_2019_1832_MOESM2_ESM.tif (8 mb)
Supplementary material 2 (TIFF 8209 kb)

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Bo Li
    • 1
  • Ryuta Saka
    • 1
  • Yuichi Takama
    • 1
  • Takehisa Ueno
    • 1
  • Yuko Tazuke
    • 1
  • Hiroomi Okuyama
    • 1
    Email author
  1. 1.Department of Pediatric SurgeryOsaka University Graduate School of MedicineSuitaJapan

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