title: Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats.
abstract: BACKGROUND
  Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation.
  
  
  METHODS
  A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria.
  
  
  RESULTS
  The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P<0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P<0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P<0.05).
  
  
  CONCLUSIONS
  Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.
authors.affiliation: Institute of General Surgical Research, Second Affiliated Hospital, Yangzhou University, Yangzhou 225001, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.forename: Pei-Jian
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Xin-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Li-De
authors.initials: LD
authors.lastname: Tao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001219:Aspartate Aminotransferases / Q000097:blood; D006085:Graft Survival / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D000860:Hypoxia / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods*; D016031:Liver Transplantation; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure; D010100:Oxygen / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010100:Oxygen