Air-ventilated normothermic machine perfusion alleviates hepatic injury from DCD rat through CYP1A2
Ji-Hua Shi,
Nuo Cheng,
Wen Zhang,
Qiang Jin,
Wen-Zhi Guo,
Guang-Bo Ge,
Shui-Jun Zhang,
Pål-Dag Line,
Yong Wang
Affiliations
Ji-Hua Shi
Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Corresponding author. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, China.
Nuo Cheng
Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
Wen Zhang
Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
Qiang Jin
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 200473, China
Wen-Zhi Guo
Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
Guang-Bo Ge
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 200473, China
Shui-Jun Zhang
Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
Pål-Dag Line
Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Yong Wang
Department of Anesthesia Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Corresponding author.
Background.Normothermic machine perfusion (NMP) could provide protection to organs from donation after circulatory death (DCD) before transplantation, and its molecular mechanism remains unclear. Our previous study discovered that the air-ventilated NMP confers a better DCD liver recovery than oxygen-ventilated NMP. The purpose in the current study was to investigate the protective mechanism of air-ventilated NMP in a rat model of DCD liver by metabolomics, and to select biomarker to predict liver function recovery.Materials and Methods.Peroxisome proliferator activator receptor-α (PPARα) agonist or antagonist was administered via the perfusion circuit in the air-ventilated NMP. Perfusate samples were taken for measurements of aminotransferases using standard biochemical methods, tumor necrosis factor-alpha and interleukin-6. Liver biopsies were allocated for detection of metabolomics, PPARα and cytochrome P450 1A2 (CYP1A2).Results.Metabolomics analysis revealed the significant increased γ-linolenic acid and decreased adrenic acid during the air-ventilated NMP, indicating linoleic acid metabolism pathway was associated with a better DCD liver recovery; as a major enzyme involved in linolenic acid metabolism, CYP1A2 was found correlated with a less inflammation and better liver function with the air-ventilated NMP; PPARα agonist could increase CYP1A2 expression and activity, decrease inflammation response, and improve liver function with the air-ventilated NMP, while PPARα antagonist played the opposite.Conclusion.Air-ventilated NMP confers a better liver recovery from DCD rats through the activated linoleic acid metabolism and CYP1A2 upregulation; CYP1A2 expression and activity might function as biomarker to predict DCD liver function recovery with NMP.
