title: NF-κB induced the donor liver cold preservation related acute lung injury in rat liver transplantation model.
abstract: BACKGROUND
  We have observed at our clinical work that acute lung injury (ALI) often occurs in patients transplanted with donor livers persevered for long time. So, we conducted this study to investigate the influence of cold preservation time (CPT) of donor liver on ALI induced by liver transplantation (LT), and further study the role of nuclear factor-κB (NF-κB) in the process.
  
  
  METHODS
  Wistar rats were used as donors and recipients to establish orthotopic rat liver transplantation models. Donor livers were preserved at 4°C for different lengths of time. The effect of NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC), on ALI was detected. All samples were harvested after 3 h reperfusion. The severity of liver injury was evaluated first. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue and liver outflow serum were measured respectively. The severity indexes of ALI, the activity of NF-κB and inhibitor-κBα (I-κBα) in lung/liver were measured accordingly.
  
  
  RESULTS
  With the prolonged liver CPT, the liver damage associated indexes and ALI-related indexes all increased significantly. TNF-α and IL-1β in liver outflow serum increased accordingly, and the activity of NF-κB in liver/lung increased correspondingly. All these ALI-associated indexes could be partially reversed by the use of PDTC.
  
  
  CONCLUSIONS
  Extended CPT aggravates the damage of donor liver and induces the expressions of TNF-α and IL-1β in liver. These inflammatory factors migrate to lung via liver outflow blood and activate NF-κB in lung, inducing ALI finally. NF-κB may play a critical role in LT-related ALI. Patients with or at risk of ALI may benefit from acute anti-inflammatory treatment with PDTC.
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: An
authors.initials: A
authors.lastname: Jiang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Quanyuan
authors.initials: Q
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D015925:Cryopreservation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha