title: Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2Areceptor mediated PI3K-Akt pathway.
abstract: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism.
  
  
  
  To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery. LY294002 was intravenously injected at 10mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2Areceptor, additional four groups were included: ZM241385 (A2Areceptor antagonist)+I/R+HCH, ZM241385+I/R, bpv(HOpic) (PTEN inhibitor)+I/R, and ZM241385+bpv+I/R+HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2Areceptor in this protection.
  
  
  
  Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic).
  
  
  
  Our findings indicate that HCH may protect the liver against I/R injury through the A2Adependent PI3K-Akt pathway.
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Ouyang
authors.initials: O
authors.lastname: Chen
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Zhouheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Rongjia
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Navy General Hospital, Beijing 100048, People's Republic of China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Junlong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: liuwenwu1980@hotmail.com.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: sunxjk@hotmail.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006859:Hydrogen / Q000008:administration & dosage*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D018047:Receptors, Purinergic P1; D006859:Hydrogen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: A(2A) receptor; Hepatic ischemia/reperfusion; High concentrations of hydrogen; Inhibitor; PI3K-Akt pathway