Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition

Int J Med Sci. 2014 Feb 11;11(4):337-43. doi: 10.7150/ijms.7861. eCollection 2014.

Abstract

Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear. This study aims to investigate possible pathomechanism of ulinastatin in reducing the inflammatory response after hepatic IR. Methods A male sprague-dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats were randomly divided into 4 groups on average, which were 0.9% saline and IR group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1 (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF-α, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology examination and apoptotic cell detection and the different expression of HMGB1 protein were also assessed. Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05). Decreased histologic damage and apoptosis were also seen in these two groups (p<0.05). Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.

Keywords: High mobility group box 1 protein (HMGB1); Ischemia reperfusion; Preconditioning; Ulinastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / metabolism
  • Cytokines / metabolism
  • Glycoproteins / pharmacology
  • Glycoproteins / therapeutic use*
  • HMGB1 Protein / metabolism*
  • Immunohistochemistry
  • Liver / metabolism*
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism*
  • Transaminases / metabolism
  • Trypsin Inhibitors / pharmacology
  • Trypsin Inhibitors / therapeutic use

Substances

  • Cytokines
  • Glycoproteins
  • HMGB1 Protein
  • Trypsin Inhibitors
  • Peroxidase
  • Transaminases
  • Aspartate Aminotransferases
  • urinastatin