机构地区:[1]Department of Hepatobiliary Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Department of General Surgery and Trauma Surgery,Children's Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China [3]Research Center of Neuroscience,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China
出 处:《Genes & Diseases》2025年第2期288-303,共16页基因与疾病(英文)
基 金:funded by the National Natural Science Foundation of China (No.82300745 to Yanyao Liu);China Postdoctoral Science Foundation (No.2023M730442 to Yanyao Liu);Chongqing Postdoctoral Science Foundation of China (No.CSTB2023NSCQ-BHX1003 to Yanyao Liu);Postdoctoral Cultivation Project of the First Affiliated Hospital of Chongqing Medical University (No.CYYY-BSHPYXM-202301 to Yanyao Liu);Chongqing Postdoctoral Innovation Talents Support Program (Chongqing,China) (No.2309013437264551 to Yanyao Liu)。
摘 要:Hepatic ischemia-reperfusion injury is an unavoidable surgical complication of liver transplantation and the leading cause of poor graft function and increased mortality post-transplantation.Multiple mechanisms have been implicated in ischemia-reperfusion injury;however,the characteristic changes at the transcriptional and metabolic levels in the early,intermediate,and late phases of ischemia-reperfusion injury remain unclear.In the study,mice underwent laparotomy following anesthesia,and the blood vessels of the liver were clipped using a vascular clamp to form 70%warm ischemia of the liver.Mouse liver sections and serum samples were collected and divided into the Sham,I1R12,11R24,and 11R48 groups.Transcriptomics and metabolomics analyses were performed to study characteristic alterations during the early,intermediate,and late phases of ischemia-reperfusion injury.Quantitative real-time PCR was used to validate the critical differentially expressed genes.The differentially expressed genes and metabolites were identified by transcriptomics and metabolomics analyses.Moreover,GO and KEGG enrichment analyses indicated that glucose metabolism remodeling,inflammatory response activation,and lipid metabolism remodeling were characteristic changes in the early,intermediate,and late phases of ischemia-reperfusion injury,respectively.In summary,our study revealed the importance of glucolipid metabolism in ischemia-reperfusion injury and provided potential therapeutic intervention targets and a new perspective to explore the underlying mechanisms of ischemia-reperfusion injury.
关 键 词:INFLAMMATION Liver ischemia-reperfusion injury Metabolic remodeling Metabolomics TRANSCRIPTOMICS
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