title: Remote ischemic preconditioning promotes early liver cell proliferation in a rat model of small-for-size liver transplantation.
abstract: BACKGROUND
  The size of the liver donor graft is a major concern in living donor liver transplantation. Rapid regeneration is essential for the survival of these grafts. The purpose of this study was to investigate the effect of remote ischemic preconditioning (RIPC) on liver regeneration in a rat small-for-size liver transplantation model.
  
  
  METHODS
  We established rat models of small-for-size liver transplantation (30%) in the presence or absence (control) of remote ischemic preconditioning. We observed liver mass regeneration, serum alanine aminotransferase, hepatic pathologic alterations, flow cytometry, and Ki-67 antigen immunohistochemistry. In addition, using Western blotting and reverse-transcriptase-polymerase chain reaction, we assessed the activation of cell cycle progression as well as tumor necrosis factor-α and interleukin-6 expression.
  
  
  RESULTS
  Compared with the control group, serum alanine aminotransferase activity was significantly lower and histopathology changes were significantly attenuated in the RIPC group. Remote ischemic preconditioning induced a high level of interleukin-6 mRNA in small grafts, but suppressed the expression of tumor necrosis factor-α. The proliferation index, indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)], was signiﬁcantly increased in the RIPC group at 24 h (58.25% ± 0.506% versus 53.405% ± 1.25%; P = .007). Meanwhile, cell cycle progression and regeneration (Ki-67) were initiated early in liver grafts treated with RIPC.
  
  
  CONCLUSIONS
  These results suggest that RIPC can protect liver cells against ischemia reperfusion injury in the small grafts and enhance liver regeneration. Interleukin-6 may be a critical mediator in the stimulatory effect on liver cell regeneration, which may make RIPC valuable as a hepatoprotective modality.
authors.affiliation: Liver Transplantation Center, First Afﬁliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.forename: Liang
authors.initials: L
authors.lastname: Gui
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Jincao
authors.initials: J
authors.lastname: Tang
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D006085:Graft Survival / Q000502:physiology; D022781:Hepatocytes / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000473:pathology* / Q000502:physiology / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology; D016031:Liver Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase