Modified mild heat shock modality attenuates hepatic ischemia/reperfusion injury

J Surg Res. 2010 Aug;162(2):213-20. doi: 10.1016/j.jss.2009.03.093. Epub 2009 May 8.

Abstract

Background: Hepatic ischemia/reperfusion (I/R) injury is a pathologic process caused by hepatic surgery and transplantation, and still remains a severe clinical problem. It was shown that preconditioning by hyperthermia might protect tissues against I/R injury. But hyperthermia could be laborious and time-consuming. Alternatively, the application of mild electrical stimulation (MES) has been reported to have positive effects in clinical settings on several medical ailments. Thus, we modified the preconditioning approach by combining short-term mild heat shock (HS) and MES, and evaluated the effect of HS+MES pretreatment on hepatic injury induced by I/R.

Materials and methods: C57BL/6J mice were sham treated or treated three times with HS (42 degrees C) and/or MES (12V) for 20min, carried out every other d within 1 wk. After the last treatment, mice were subjected to hepatic ischemia for 30 or 60min and reperfusion for 6h. Liver injury was assessed by evaluating the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The expressions of pro-inflammatory cytokines and heat shock protein (Hsp) 72 in liver tissues were also assessed by real-time PCR and Western blotting analyses, respectively.

Results: HS+MES pretreatment suppressed the hepatic I/R-induced release of serum AST and ALT and the mRNA levels of some pro-inflammatory cytokines. In addition, HS+MES up-regulated the expression of Hsp72 in mice liver.

Conclusions: HS+MES preconditioning ameliorated hepatic I/R injury possibly through Hsp72 induction, and suppressed pro-inflammatory cytokine expression in mice liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Cytokines / genetics
  • DNA Primers
  • Electric Stimulation* / instrumentation
  • Electric Stimulation* / methods
  • Gene Amplification
  • Gene Expression Regulation
  • HSP72 Heat-Shock Proteins / genetics
  • Hot Temperature*
  • Ischemia / physiopathology*
  • Ischemia / prevention & control
  • Liver / injuries
  • Liver / pathology
  • Liver / surgery
  • Liver Circulation
  • Liver Transplantation / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Postoperative Complications / epidemiology
  • Reperfusion Injury / physiopathology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cytokines
  • DNA Primers
  • HSP72 Heat-Shock Proteins
  • Aspartate Aminotransferases
  • Alanine Transaminase