Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway

PeerJ

article

Tianliang Hou¹  Haiping Ma¹  Haixia Wang²  Chunling Chen¹  Jianrong Ye¹  Ahmed Mohamed Ahmed³  Hong Zheng¹ 

[1] Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University;Department of Mastology, Xinjiang Maternal and Child Health Hospital;Department of Intensive Care Unit ,(ICU), Yardimeli Hospital

关键词: Sevoflurane preconditioning;    Myocardial protective effect;    Hypoxia-inducible factor-1;    Glycolysis;    Hypoxia/reoxygenation injury;    Pyruvate dehydrogenase kinase-1;   

DOI  :  10.7717/peerj.10603

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundSevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning (IPC). However, the underlying molecular mechanism of SPC remains unclear. Studies confirm that hypoxia-inducible factor-1 (HIF-1) can transform cells from aerobic oxidation to anaerobic glycolysis by activating the switch protein pyruvate dehydrogenase kinase-1 (PDK-1), thus providing energy for the normal life activities of cells under hypoxic conditions. The purpose of this study was to investigate whether the cardioprotective effects of SPC are associated with activation of the HIF-1a/PDK-1 signal pathway.MethodsThe H9c2 cardiomyocytes hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the end of equilibration. Lactate dehydrogenase (LDH) level, cell viability, cell apoptosis, mitochondrial membrane potential, key enzymes of glycolysis, ATP concentration of glycolysis were assessed after the intervention. Apoptosis related protein(Bcl-2, Bax), HIF-1a protein, and PDK-1 protein were assessed by western blot.ResultsCompared with the H/R group, SPC significantly increased the expression of HIF-1a, PDK-1, and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the apoptosis ratio and Lactate dehydrogenase (LDH) level, increasing the cell viability, content of key enzymes of glycolysis, ATP concentration of glycolysis and stabilizing the mitochondrial membrane potential. However, the cardioprotective effects of SPC were disappeared by treatment with a HIF-1a selective inhibitor.ConclusionThis study demonstrates that the cardioprotective effects of SPC are associated with the activation of the HIF-1a/PDK-1 signaling pathway. The mechanism may be related to increasing the content of key enzymes and ATP of glycolysis in the early stage of hypoxia.

【 授权许可】

CC BY