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肝脏移植中线粒体靶向策略的最新见解。

Recent insights into mitochondrial targeting strategies in liver transplantation.

机构信息

Department of Surgery, Instituto Português de Oncologia de Coimbra, Coimbra, Portugal.

Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal; and Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.

出版信息

Int J Med Sci. 2018 Jan 8;15(3):248-256. doi: 10.7150/ijms.22891. eCollection 2018.

Abstract

Ischemia/reperfusion (I/R) injury in liver transplantation can disrupt the normal activity of mitochondria in the hepatic parenchyma. This potential dysfunction of mitochondria after I/R injury could be responsible for the initial poor graft function or primary nonfunction observed after liver transplantation. Thus, determining the mechanisms that lead to human hepatic mitochondrial dysfunction might contribute to improving the outcome of liver transplantation. Furthermore, early identification of novel prognostic factors involved in I/R injury could serve as a key endpoint to predict the outcome of liver grafts and also to promote the early adoption of novel strategies that protect against I/R injury. Here, we briefly review recent advances in the study of mitochondrial dysfunction and I/R injury, particularly in relation to liver transplantation. Next, we highlight various pharmacological therapeutic strategies that could be applied, and discuss their relationship to relevant mitochondrion-related processes and targets. Lastly, we note that although considerable progress has been made in our understanding of I/R injury and mitochondrial dysfunction, further investigation is required to elucidate the cellular and molecular mechanisms underlying these processes, thereby identifying biomarkers that can help in evaluating donor organs.

摘要

肝移植中的缺血/再灌注(I/R)损伤会破坏肝实质中线粒体的正常活动。这种 I/R 损伤后线粒体的潜在功能障碍可能是肝移植后观察到的初始移植物功能不良或原发性无功能的原因。因此,确定导致人类肝线粒体功能障碍的机制可能有助于改善肝移植的结果。此外,早期确定与 I/R 损伤相关的新预后因素可以作为预测肝移植物预后的关键终点,并促进采用新的策略来预防 I/R 损伤。在这里,我们简要回顾了线粒体功能障碍和 I/R 损伤研究的最新进展,特别是与肝移植相关的研究进展。接下来,我们强调了可以应用的各种药理学治疗策略,并讨论了它们与相关线粒体相关过程和靶点的关系。最后,我们注意到,尽管我们对 I/R 损伤和线粒体功能障碍的理解已经取得了相当大的进展,但仍需要进一步研究来阐明这些过程的细胞和分子机制,从而确定有助于评估供体器官的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0280/5820854/cbe539beed87/ijmsv15p0248g001.jpg

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