Donor Brain Death Leads to a Worse Ischemia-Reperfusion Injury and Biliary Injury After Liver Transplantation in Rats.

Brain-dead (BD) donor is the main source for liver transplantation (LT). We aim to investigate the effect of brain death on donor liver inflammatory activity and its association with ischemia-reperfusion (I/R) injury and biliary tract injury after LT. A brain death model using male Lewis rats was established, in both BD and non-BD groups; livers were harvested for transplantation using a 2-cuff technique. The rats were sacrificed 12 hours (n = 10) or 4 weeks (n = 10) after transplantation. I/R injury and long-term biliary tract injury were observed after transplantation. All rats survived for 4 weeks after transplantation. At 12 hours after BD-donor LT (BDDLT), liver injury worsened; serum transaminases, bilirubin, oxidative stress, inflammatory responses and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining level substantially increased (P <.05). At 4 weeks after BDDLT, serum bilirubin and bile lactate dehydrogenase and γ-glutamyl transpeptidase levels were elevated (P <.05). Biliary fibrosis and epithelial-mesenchymal transition (EMT) were detectable and NDRG1 gene expression was decreased. These results suggested that brain death–induced inflammatory response in donor organs and resulted in a worse I/R injury and biliary tract injury after LT in rats. The brain death–related biliary tract injury may be associated with the regulation of EMT through NDRG1. • Brain death activated liver inflammation in rats. • Brain death was related to ischemia-reperfusion injury after liver transplantation in rats. • Brain death was associated with biliary tract injury after transplantation in rats. • NDRG1 -mediated epithelial-mesenchymal transition in cholangiocytes after brain-dead donor liver transplantation. [ABSTRACT FROM AUTHOR]