Therapeutic hypothermia attenuates liver injury in polymicrobial sepsis model of rats via Akt survival pathway.
BACKGROUND
Therapeutic hypothermia has been proposed to protect organs in some diseases. However, the effect of therapeutic hypothermia on liver injury in sepsis is unknown. The aim of this study was to evaluate the effects of therapeutic hypothermia on liver injury in sepsis.


METHODS
Male Sprague-Dawley rats underwent cecal ligation and incision (CLI). We randomly allocated rats into one of two groups 1 h after CLI: hypothermia (HT) and normothermia (NT). In the HT group, body temperature decreased to 32°C ± 0.5°C and was maintained 4 h, followed by rewarming to 37°C for 2 h. In the NT group, body temperature was maintained at 37°C ± 0.5°C throughout the experimental periods. At 7 h after CLI, we harvested blood and liver tissues and measured serum alanine aminotransferase and the histological liver injury score. We performed immunohistochemistry for cleaved caspase-3 and evaluated phosphorylation of Akt, GSK-3β and Bad with the Western blot assay.


RESULTS
Serum alanine aminotransferase was significantly lower in the HT group than in the NT group (57.0 ± 6.0 IU/L versus 192.5 ± 92.5 IU/L; P = 0.028). The histological liver injury score was also significantly lower in the HT group than in the NT group (2.9 ± 0.5 versus 5.4 ± 0.6; P = 0.016). Phosphorylation of Akt, GSK-3β, and Bad was significantly increased in the HT group compared with the NT group (P < 0.001, P = 0.007, and P = 0.001, respectively). Hypothermia significantly mitigated expression of cleaved caspase-3 compared with the NT group (P = 0.032).


CONCLUSIONS
Therapeutic hypothermia attenuated liver injury in a polymicrobial sepsis model of rats by enhancing the Akt signaling pathway and decreasing apoptosis.
Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.
Jae Hyuk
JH
Lee
Kyuseok
K
Kim
You Hwan
YH
Jo
Min A
MA
Kim
Kwang Pil
KP
Rim
Kyeong Won
KW
Kang
Joong Eui
JE
Rhee
Min Ji
MJ
Lee
Hyun Sook
HS
Lee
Woon Yong
WY
Kwon
Gil Joon
GJ
Suh
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D007036:Hypothermia, Induced; D008099:Liver / Q000473:pathology*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000628:therapy*; D015398:Signal Transduction
D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt