Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury

Clin Res Hepatol Gastroenterol. 2015 Oct;39(5):610-9. doi: 10.1016/j.clinre.2014.12.012. Epub 2015 Feb 25.


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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Ischemic Preconditioning*
  • Liver Transplantation*
  • Mitochondria / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Signal Transduction


  • Biomarkers
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Glucose