肝移植返老还童中的靶向缺血再灌注损伤

Q4 Medicine

Transplantation Reports Pub Date : 2025-02-26 DOI:10.1016/j.tpr.2025.100176

Kenneth J. Dery, Fady Kaldas, Jerzy W. Kupiec-Weglinski

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引用次数: 0

摘要

背景肝脏缺血再灌注损伤（HIRI）是一个多方面的病理生理过程，涉及一连串相互关联的细胞事件。最初的缺血应激，随后肝脏血液循环的重建，引发了前馈性先天性免疫驱动反应，加剧了肝细胞损伤。肝细胞损伤是肝移植（LT）的一个重大临床挑战，因为它可能导致组织损伤、器官功能障碍和不良的临床结果。它探讨了促进 HIRI 后体内平衡调节的机制。此外，它还探讨了旨在减轻氧化应激和炎症的精细药理策略。HIRI 研究的热门话题领域包括自噬、循环死亡后的捐赠以及 LT 后 NLRP3 依赖性炎性体的激活。目前正在探索新的药理制剂，如抗氧化化合物、代谢调节剂和植物提取的化合物，以影响炎症反应。临床上非常重视利用边缘供体移植物和先进的机器灌注技术来扩大供体库。通过开发与人体相关的器官组织或体内外肝脏灌注系统来加强转化研究，对于将实验室发现与挽救生命的外科手术的临床实践联系起来至关重要。结论强调细胞对氧应激和免疫细胞激活反应的调控机制的综合方法，以及创新的供体器官保存方法（如机器灌注），将通过提高移植物的存活率和活化次优供体器官来塑造未来的 HIRI 研究方向。

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Targeting Ischemia-reperfusion injury in liver transplant rejuvenation

Background

Hepatic ischemia-reperfusion injury (HIRI) is a multifaceted pathophysiological process involving a cascade of interconnected cellular events. The initial ischemic stress, followed by the reestablishment of blood circulation to the liver, triggers a feed-forward innate immune-driven response that exacerbates the hepatocellular injury. HIRI poses a significant clinical challenge in liver transplantation (LT), as it can result in tissue damage, organ dysfunction, and poor clinical outcomes.

Methods and results

This review highlights current key issues in HIRI translational research, as revealed by recent bibliometric studies. It examines the mechanisms that facilitate homeostatic regulation after HIRI. Additionally, it addresses refined pharmacological strategies aimed at mitigating oxidative stress and inflammation. Hot topic areas in HIRI research include autophagy, donation after circulatory death, and NLRP3-dependent inflammasome activation following LT. New pharmacological agents, such as anti-oxidative compounds, metabolic modulators, and plant-derived compounds, are being explored to influence inflammatory responses. There is a strong clinical emphasis on broadening the donor pool by utilizing marginal donor grafts and advanced machine perfusion techniques. Enhancing translational research through the development of human-relevant organoids or ex vivo liver perfusion systems is essential for connecting laboratory discoveries with clinical practices in life-saving surgical procedures.

Conclusion

A comprehensive approach that emphasizes the regulatory mechanisms of cellular responses to oxygen stress and immune cell activation, alongside innovative donor organ preservation, like machine perfusion, will shape the future direction of HIRI research by enhancing graft viability and revitalizing suboptimal donor organs.

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来源期刊

Transplantation Reports Medicine-Transplantation

CiteScore

0.60

自引率

0.00%

发文量

审稿时长

101 days

期刊介绍： To provide to national and regional audiences experiences unique to them or confirming of broader concepts originating in large controlled trials. All aspects of organ, tissue and cell transplantation clinically and experimentally. Transplantation Reports will provide in-depth representation of emerging preclinical, impactful and clinical experiences. -Original basic or clinical science articles that represent initial limited experiences as preliminary reports. -Clinical trials of therapies previously well documented in large trials but now tested in limited, special, ethnic or clinically unique patient populations. -Case studies that confirm prior reports but have occurred in patients displaying unique clinical characteristics such as ethnicities or rarely associated co-morbidities. Transplantation Reports offers these benefits: -Fast and fair peer review -Rapid, article-based publication -Unrivalled visibility and exposure for your research -Immediate, free and permanent access to your paper on Science Direct -Immediately citable using the article DOI