Li Qi, Qin Xiaoyan, Wang Liangxu, Hu Dingheng, Liao Rui, Yu Huarong, Wu Zhongjun, Liu Yanyao
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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.
Genes Dis. 2024 Nov 17;12(2):101465. doi: 10.1016/j.gendis.2024.101465. eCollection 2025 Mar.
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, I1R24, and I1R48 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.
肝缺血再灌注损伤是肝移植不可避免的手术并发症，也是移植后移植物功能不良和死亡率增加的主要原因。缺血再灌注损伤涉及多种机制；然而，缺血再灌注损伤早期、中期和晚期在转录和代谢水平的特征性变化仍不清楚。在该研究中，小鼠在麻醉后进行剖腹手术，使用血管夹夹住肝脏血管以形成70%的肝脏热缺血。收集小鼠肝脏切片和血清样本，并分为假手术组、缺血1小时再灌注12小时组、缺血1小时再灌注24小时组和缺血1小时再灌注48小时组。进行转录组学和代谢组学分析以研究缺血再灌注损伤早期、中期和晚期的特征性改变。采用定量实时PCR验证关键差异表达基因。通过转录组学和代谢组学分析鉴定差异表达基因和代谢物。此外，基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，葡萄糖代谢重塑、炎症反应激活和脂质代谢重塑分别是缺血再灌注损伤早期、中期和晚期的特征性变化。总之，我们的研究揭示了糖脂代谢在缺血再灌注损伤中的重要性，并提供了潜在的治疗干预靶点以及探索缺血再灌注损伤潜在机制的新视角。
