The protective effect of moderate hypothermia during intestinal ischemia-reperfusion is associated with modification of hepatic transcription factor activation.
OBJECTIVE
Moderate hypothermia throughout intestinal ischemia-reperfusion (IIR) injury reduces multiple organ dysfunction. Heat shock proteins (HSPs) have been shown to be protective against ischemia-reperfusion injury, and STAT (Signal Transducers and Activators of Transcription) proteins are pivotal determinants of the cellular response to reperfusion injury. The aim of this study is to investigate the mechanism of hypothermic protection during IIR.


METHODS
Adult rats underwent intestinal ischemia-reperfusion (IIR), 60-minute ischemia and 60-minute reperfusion, or sham (120 minutes) at either normothermia or moderate hypothermia. Four groups of animals were studied: (1) normothermic sham (NS), (2) normothermic IIR (NIIR), (3) hypothermic sham (HS), and (4) hypothermic IIR (HIIR). Western blotting measured heat shock protein expression, phosphorylated (p-) and total (T-) hepatic STAT-1 and STAT-3.


RESULTS
There were no differences in expression of HSPs 27, 47, 60, i70, c70, or 90 between any of the experimental groups. NIIR caused a significant increase in p-STAT-1 compared with normothermic sham (P <.05) and a highly significant increase in p-STAT-3 (P <.001), both these increases were completely abolished by moderate hypothermia (P <.01 v NIIR.)


CONCLUSIONS
The protective effect of moderate hypothermia on liver is not mediated by HSP expression at this time-point. Hypothermia may act by decreasing hepatic STAT activation, supporting the potential therapeutic role of moderate hypothermia. Modulation of STAT activation may also provide novel therapeutic targets.
Parkinson
E J
EJ
Department of Paediatric Surgery, Institute of Child Health, London, England, UK.
Townsend
P A
PA
Stephanou
A
A
Latchman
D S
DS
Eaton
S
S
Pierro
A
A
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007036:Hypothermia, Induced; D008099:Liver / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000628:therapy; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators