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

Clinics and Research in Hepatology and Gastroenterology
Zhuang ZhuonanXu Kesen

Abstract

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. 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. 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 sign...Continue Reading

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Citations

Dec 26, 2017·Nutrition and Healthy Aging·Sadeesh K Ramakrishnan, Yatrik M Shah
Dec 2, 2021·Experimental and Therapeutic Medicine·Xiaoyang Lan, Yumin Xu

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