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

Sanyang Chen; Hongbo Fang; Jie Li; Ji-Hua Shi; Jiakai Zhang; Peihao Wen; Zhihui Wang; Shengli Cao; Han Yang; Jie Pan; Hongwei Tang; Huapeng Zhang; Wenzhi Guo; Shuijun Zhang

doi:10.1016/j.transproceed.2019.10.012

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

Transplant Proc. 2020 Jan-Feb;52(1):373-382. doi: 10.1016/j.transproceed.2019.10.012. Epub 2020 Jan 16.

Authors

Sanyang Chen¹, Hongbo Fang², Jie Li², Ji-Hua Shi¹, Jiakai Zhang², Peihao Wen², Zhihui Wang², Shengli Cao², Han Yang², Jie Pan², Hongwei Tang¹, Huapeng Zhang¹, Wenzhi Guo¹, Shuijun Zhang³

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Henen Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery Digestive Organ Transplantation at Henan University, Zhengzhou, Henan Province, China; Zheng Zhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan Province, China.
² Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
³ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Henen Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery Digestive Organ Transplantation at Henan University, Zhengzhou, Henan Province, China; Zheng Zhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan Province, China. Electronic address: zhangshuijun@zzu.edu.cn.

PMID: 31955852
DOI: 10.1016/j.transproceed.2019.10.012

Abstract

Background: 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.

Material and method: 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.

Results: 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.

Conclusions: 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.

MeSH terms

Animals
Brain Death*
Liver / metabolism
Liver / pathology*
Liver Transplantation / methods*
Male
Rats
Rats, Inbred Lew
Reperfusion Injury / metabolism
Reperfusion Injury / pathology*
Tissue Donors* / supply & distribution