Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury.
BACKGROUND
Ischemia and reperfusion (I/R) injury is one of the main lesions after liver transplantation. This study aims to detect hypoxia-induced HIF-1α protects transplanted liver against I/R injury by promoting glucose metabolism to decrease mitochondrial injury and apoptosis on rat model.


METHODS
The rats were given a treatment of 90 min non-lethal hypoxic preconditioning to induce and increase the HIF-1α expression. The autologous orthotopic liver transplantation model was used to imitate liver I/R injury.


RESULTS
Hypoxic-induced HIF-1α was detected to increase in liver tissue after 90-minute hypoxic environment (HP vs. Ctrl, *P<0.001). After operation, the expression of HIF-1α in liver tissue was also stayed at a high level. At 24h after operation, several genes were promoted, such as the levels of HK-2 (HP vs. AT, 24h, *P=0.004), Lactate dehydrogenase (LDHA) (HP vs. AT, 24h, *P=0.003), pyruvate dehydrogenase kinase (PDK-1) (HP vs. AT, 24h, *P=0.007), even the NF-κB and Erk pathways. From the TUNEL assay, the apoptosis in hypoxic preconditioning liver tissue was decreased compared with non-HP operative group at 12h after operation. The expressions of cleaved-caspase 3 (HP vs. AT, *P=0.0119) and PARP (HP vs. AT, *P=0.0134) in HP group were also significantly lower than AT group.


CONCLUSIONS
The hypoxia-induced HIF-1α could promote glucose metabolism to protect hepatocellular mitochondria from damage. It could be a useful way to protect liver against I/R injuries and inflammatory injury, and particularly promote the recovery of graft function.
Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, 250000 Jinan, China.
Zhuang
Z
Zhuonan
Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, 250000 Jinan, China.
Guo
G
Sen
Department of General Surgery, the Second Hospital of Shandong University, 250033 Jinan, China.
Ji
J
Zhipeng
Department of Neurology, Rizhao First People Hospital, 276800 Rizhao, China.
Zhuang
Z
Maoyou
Department of Surgery, the Traditional Chinese Medical Hospital of Yangzhou University, 225001 Yangzhou, China.
Yin
Y
Linglan
Department of Pathology, Rizhao First People Hospital, 276800 Rizhao, China.
Wang
W
Gangping
Research Institute of General Surgery, the Second Affiliated Clinical Hospital of Yangzhou University, 225001 Yangzhou, China; Department of Hepatobiliary Pancreatic Center, The Third Hospital Affiliated to Nantong University, Wuxi, 214041, Jiangsu, China.
Jin
J
Cheng
Research Institute of General Surgery, the Second Affiliated Clinical Hospital of Yangzhou University, 225001 Yangzhou, China.
Meng
M
Zhongliang
Department of Thoracic medical oncology, MD Anderson Cancer Center, University of Texas, Houston, 77030 TX, United States.
Jessie
J
Tian
Research Institute of General Surgery, the Second Affiliated Clinical Hospital of Yangzhou University, 225001 Yangzhou, China. Electronic address: yzu.edu.pjz@163.com.
Zhang
Z
Peijian
Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, 250000 Jinan, China. Electronic address: xukesen@163.com.
Xu
X
Kesen
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D019194:Ischemic Preconditioning; D016031:Liver Transplantation; D008928:Mitochondria / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction
D015415:Biomarkers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005947:Glucose