Hypothermic Machine Perfusion Protects Donation After Cardiac Deathliver Graft Through Gstm1-mediated Cytochrome P450 Exogenous Substance Metabolism Pathway
Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases, Wuhan, China
Meeting: 2019 American Transplant Congress
Abstract number: B10
Keywords: Donors, non-heart-beating, Ischemia, Machine preservation, Protective genes
Session Information
Session Name: Poster Session B: Ischemia Reperfusion & Organ Rehabilition
Session Type: Poster Session
Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Donation after cardiac death (DCD) is the mainly resource to relieve organ-transplantation shortage. Our previous research have confirmed that the function of DCD liver grafts can be well preserved by using Hypothermic machine perfusion(HMP) so as to get a significantly transplantation outcome, however, the mechanism in it is unknown.
*Methods: We collected liver freezing tissues of three CS human liver grafts and three human liver grafts with 2 hours HMP and then detected the gene expression with BGISEQ-500-RNAseq technique, GO and KEGG pathway enrichment analysis were used to detect the notable pathway, the differentiation genes were analyzed for further research. Besides, western blot was used to verified the differentiation genes corresponding proteins in the most notable pathway. We further validated the expression of the above differential gene-related proteins by constructing DCD model in Sprague Dawley (SD) rat.
*Results: BGISEQ-500-RNAseq data showed that more than one hundred of genes had more than 5-fold change in these two groups, GO and KEGG pathway enrichment analysis revealed that more than nineteen pathways had statistical significance (P<0.05), while, the most notable one is the metabolism of xenobiotics by cytochrome P450. Then, we further detected the corresponding proteins in this pathway, it showed that AKR1B10, CYP2A6 were down-expression, while CYP1A2 was up-expression in HMP groups. The protein expression of SD rat model showed that compared with CS group, GSTM1, CYP2A6 and AKR1B10 were increased in MHP group before and after reperfusion.
*Conclusions: we have confirmed that the GSTM1-mediated cytochrome P450 exogenous substance metabolism pathway was the the most notable pathway, and the corresponding proteins detecting also verified, while this pathway is mainly to slow the production of oxidative stress substances in liver ischemia-reperfusion injury, thereby alleviating the warm ischemic injury of DCD donor liver. So we concluded that HMP can protect DCD liver graft through this pathway.
To cite this abstract in AMA style:
Liang W, Ye S, Zhong Z, Hu Q, Wang Y, Ye Q. Hypothermic Machine Perfusion Protects Donation After Cardiac Deathliver Graft Through Gstm1-mediated Cytochrome P450 Exogenous Substance Metabolism Pathway [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/hypothermic-machine-perfusion-protects-donation-after-cardiac-deathliver-graft-through-gstm1-mediated-cytochrome-p450-exogenous-substance-metabolism-pathway/. Accessed May 11, 2025.« Back to 2019 American Transplant Congress