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在猪缺血再灌注损伤模型的离体肝脏灌注过程中进行全面胆汁酸池分析。

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury.

机构信息

Department of General Surgery and Liver Transplantation, Croix Rousse University Hospital, Lyon, France.

Department of Pediatric Surgery and Liver Transplantation, Femme Mere Enfant University Hospital, Lyon, France.

出版信息

Sci Rep. 2024 Jan 29;14(1):2384. doi: 10.1038/s41598-024-52504-7.

DOI:10.1038/s41598-024-52504-7
PMID:38286808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10824768/
Abstract

Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.

摘要

胆汁酸 (BA) 是肝脏再生和损伤的关键。本研究旨在分析缺血再灌注 (IRI) 引起的 BA 池变化，并研究与静态冷保存 (SCS) 相比，低温氧合灌注 (HOPE) 对 BA 池的影响。在猪 IRI 模型中，肝移植物经历 30 分钟无心跳热缺血，随后进行 6 小时 SCS(n = 6)±2 小时 HOPE(n = 6)和 2 小时离体温热再灌注。使用液相色谱-串联质谱法分析胆汁样本中的 BA 池。我们鉴定了 16 种 BA，并观察到对缺血再灌注的反应发生了显著变化，这些变化与保护和损伤机制有关。其次，与 SCS 相比，HOPE 处理的肝移植物表现出更具保护作用的 BA 表型，其特征是更亲水的 BA 池。关键 BA，如甘氨胆酸，被鉴定出来，并与再灌注期间转氨酶释放减少和乳酸清除改善相关。偏最小二乘判别分析显示 HOPE 组具有明显的损伤特征。总之，BA 池随肝移植物 IRI 而变化，与 HOPE 保存相比，SCS 可导致保护作用的 BA 表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/2d7f193730e7/41598_2024_52504_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/ff34a1895b99/41598_2024_52504_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/185b1493c111/41598_2024_52504_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/771090fa3fde/41598_2024_52504_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/399ea0c4e0de/41598_2024_52504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/2d7f193730e7/41598_2024_52504_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/ff34a1895b99/41598_2024_52504_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/185b1493c111/41598_2024_52504_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/771090fa3fde/41598_2024_52504_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/399ea0c4e0de/41598_2024_52504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/10824768/2d7f193730e7/41598_2024_52504_Fig5_HTML.jpg

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Transplantation. 2023 May 1;107(5):e125-e126. doi: 10.1097/TP.0000000000004530. Epub 2023 Mar 1.
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Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion.
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A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.多中心随机对照试验研究低温氧合灌注（HOPE）在人类肝移植前对供体肝脏的作用。
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