title: Hyperbaric Oxygen Preconditioning Attenuates Myocardium Ischemia-Reperfusion Injury Through Upregulation of Heme Oxygenase 1 Expression: PI3K/Akt/Nrf2 Pathway Involved.
abstract: BACKGROUND
  With the rise of the burden of ischemic heart disease, both clinical and economic evidence show a desperate need to protect the heart against myocardium ischemia-reperfusion injury-related complications following cardiac surgery or percutaneous coronary intervention. However, there is no effective intervention for myocardium ischemia-reperfusion injury as yet.
  
  
  METHODS
  We pretreated mice with 4 daily 2.0 absolute atmosphere (ATA) hyperbaric oxygen, then observed its effects on heart function parameters and infarct size following in situ ischemia-reperfusion. Multiple oxidative and inflammation products were measured in the myocardium. Next, we investigated the expression of heme oxygenase 1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt) pathway, and NF-E2-related factor 2 (Nrf2) in the presence of myocardium ischemia-reperfusion injury, hyperbaric oxygen preconditioning, and their inhibitors and their effects on heart function parameters.
  
  
  RESULTS
  Hyperbaric oxygen preconditioning ameliorated the cardiac function and histological alterations induced by myocardium ischemia-reperfusion injury, decreased oxidative products and proinflammatory cytokine. Hyperbaric oxygen preconditioning increased expression of HO-1, which was suppressed by PI3K inhibitor LY294002, Nrf2 knockout, and Akt inhibitor triciribine. The expression of Nrf2 was enhanced by hyperbaric oxygen preconditioning, but decreased by LY294002 and triciribine. The Akt was also activated by hyperbaric oxygen preconditioning but suppressed by LY294002. The hemodynamic assays showed that cardiac function was suppressed by LY294002, Nrf2 knockout, and triciribine.
  
  
  CONCLUSIONS
  These data present a novel signaling mechanism by which hyperbaric oxygen preconditioning protects myocardium ischemia-reperfusion injury via PI3K/Akt/Nrf2-dependent antioxidant defensive system.
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of General Medicine, The Fourth Hospital of Heilongjiang Province, Harbin, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Zhongqiao
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China kanzhaoharbin@sina.com.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006931:Hyperbaric Oxygenation / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000628:therapy*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002867:Chromones; D009025:Morpholines; D051267:NF-E2-Related Factor 2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051547:Heme Oxygenase-1; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Nrf2; PI3K/Akt; heme oxygenase 1; hyperbaric oxygen preconditioning; myocardium ischemia-reperfusion injury