Mild Hypothermia Pretreatment Attenuates Liver Ischemia Reperfusion Injury Through Inhibiting c-Jun NH2-terminal Kinase Phosphorylation in Rats

Abstract Background Mild hypothermia is known to be protected against ischemia reperfusion (IR) injury. But the exact mechanisms of protection have not yet been fully understood and its usage has been limited. Mild hypothermia pretreatment (MHP) is used to investigate the mechanisms of the protective effects against liver IR injury. Methods Anesthetized male Sprague-Dawley rats were randomly divided into five groups including the normal group (N), sham group (S), MHP group, normothermia pretreatment (NP) + IR group, and the MHP + IR group. In the pretreatment groups, mild hypothermia (32.2 ± 0.3°C) and normothermia (37 ± 0.5°C) pretreatment were applied for 2 hours, respectively. Then the IR groups suffered partial (70%) hepatic ischemia for 1 hour and reperfusion for 6 hours. At last, hepatic injury, apoptosis, and protein expression were assessed. Results Levels of serum alanine transaminase, hepatic injury, hepatocyte apoptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were significantly higher in the IR groups. But when compared to NP, all these changes induced by IR were markedly attenuated by MHP. Serum alanine transaminase levels were 383.4 ± 13.1U/L in the MHP + IR group and 951.3 ± 39.4 U/L in the NP + IR group. The histologic score of liver injury in the MHP + IR group was 4.83 ± 1.17, whereas in the NP + IR group it was 10.5 ± 1.05. The proportion of apoptotic cells in the MHP + IR group was 11.58 ± 0.60, but in the NP + IR group, it was 44.95 ± 1.61. The phosphorylation of JNK was also significantly reduced in the MHP + IR group. All these differences are statistically significant ( P Conclusions MHP could markedly reduce liver IR injury, and these protective effects may be mainly exerted via inhibition of JNK phosphorylation.