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

Summary 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 vs. AT, 24 h, * P  = 0.004), Lactate dehydrogenase (LDHA) (HP vs. AT, 24 h, * P  = 0.003), pyruvate dehydrogenase kinase (PDK-1) (HP vs. AT, 24 h, * 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 12 h 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.