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Mol Med Rep. 2017 Nov;16(5):7520-7526. doi: 10.3892/mmr.2017.7501. Epub 2017 Sep 18.

Mild hypothermia pretreatment protects against liver ischemia reperfusion injury via the PI3K/AKT/FOXO3a pathway.

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Department of Transplant Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, Hunan 410013, P.R. China.
Department of Transplant Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei 430071, P.R. China.


Mild hypothermia is known to protect against ischemia and reperfusion (IR) injury. The exact mechanisms of the protection are not fully understood. Forkhead box O3 (FOXO3a) has been defined as a critical mediator in cellular processes, including oxidative stress, apoptosis, inflammation, cell death and DNA repair; however, the protection function in mild hypothermia has not been reported previously. The current study was designed to investigate the function of phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/FOXO3a pathway in pretreatment with mild hypothermia during IR injury. Additionally, PI3K/AKT/FOXO3a signaling was inhibited using Ly294002 and the effect on the protective function of mild hypothermia pretreatment was evaluated. Furthermore, the apoptotic and inflammatory response induced by the IR injury was evaluated. Liver IR injury induced a significant increase in the level of apoptosis and inflammatory responses. However, pretreatment with mild hypothermia increased phospho (p)‑AKT and p‑FOXO3a following IR injury, and significantly reduced apoptosis and inflammatory cytokines release. However, inhibiting p‑AKT and p‑FOXO3a using Ly294002 suppressed the liver protection produced by mild hypothermia. In conclusion, these findings indicated that mild hypothermia pretreatment exhibited liver protective effects against IR injury associated with suppressing inflammatory cytokine release and apoptosis via the PI3K/AKT/FOXO3a pathway.

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