Department of Surgery, Experimental Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
BIH Academy, Clinician Scientist Program, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
Eur J Med Res. 2024 Jul 11;29(1):361. doi: 10.1186/s40001-024-01961-x.
Liver grafts are frequently declined due to high donor age or age mismatch with the recipient. To improve the outcome of marginal grafts, we aimed to characterize the performance of elderly vs. young liver grafts in a standardized rat model of normothermic ex vivo liver machine perfusion (NMP).
Livers from Sprague-Dawley rats aged 3 or 12 months were procured and perfused for 6 h using a rat NMP system or collected as a reference group (n = 6/group). Tissue, bile, and perfusate samples were used for biochemical, and proteomic analyses.
All livers cleared lactate during perfusion and continued to produce bile after 6 h of perfusion (614 mg/h). Peak urea levels in 12-month-old animals were higher than in younger animals. Arterial and portal venous pressure, bile production and pH did not differ between groups. Proteomic analysis identified a total of 1477 proteins with oxidoreductase and catalytic activity dominating the gene ontology analysis. Proteins such as aldehyde dehydrogenase 1A1 and 2-Hydroxyacid oxidase 2 were significantly more present in livers of older age.
Young and elderly liver grafts exhibited similar viability during NMP, though proteomic analyses indicated that older grafts are less resilient to oxidative stress. Our study is limited by the elderly animal age, which corresponds to mature but not elderly human age typically seen in marginal human livers. Nevertheless, reducing oxidative stress could be a promising therapeutic target in the future.
由于供体年龄较高或与受者年龄不匹配，经常会拒绝肝脏移植物。为了提高边缘供体移植物的预后，我们旨在通过标准的大鼠常温离体肝脏机器灌注（NMP）模型来描述老年与年轻供体肝脏的性能。
从 3 个月或 12 个月大的 Sprague-Dawley 大鼠中获取肝脏，并使用大鼠 NMP 系统进行 6 小时灌注，或作为参考组进行采集（每组 n=6）。对组织、胆汁和灌流液样本进行生化和蛋白质组学分析。
所有肝脏在灌注过程中清除了乳酸，并在灌注 6 小时后继续产生胆汁（614mg/h）。12 个月大动物的峰值尿素水平高于年轻动物。动脉和门静脉压、胆汁生成和 pH 在各组之间没有差异。蛋白质组学分析共鉴定出 1477 种蛋白质，氧化还原酶和催化活性占据了基因本体分析的主导地位。醛脱氢酶 1A1 和 2-羟酸氧化酶 2 等蛋白质在老年肝脏中明显更为丰富。
在 NMP 过程中，年轻和老年供体肝脏表现出相似的活力，但蛋白质组学分析表明，老年供体肝脏对氧化应激的抵抗力较弱。我们的研究受到老年动物年龄的限制，这与通常在边缘供体人类肝脏中看到的成熟但非老年人类年龄相对应。然而，降低氧化应激可能是未来有前途的治疗靶点。
