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微小RNA:肝脏缺血再灌注损伤中的新靶点

MicroRNAs: Novel Targets in Hepatic Ischemia-Reperfusion Injury.

作者信息

Ingram Holly, Dogan Murat, Eason James D, Kuscu Cem, Kuscu Canan

机构信息

Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, School of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Biomedicines. 2022 Mar 29;10(4):791. doi: 10.3390/biomedicines10040791.

Abstract

Hepatic ischemia-reperfusion injury (IRI) is one of the main factors for early allograft dysfunction (EAD), which may lead to graft rejection, graft loss, or shortened graft life in liver transplantation. Hepatic IRI appears to be inevitable during the majority of liver procurement and transportation of donor organs, resulting in a cascade of biological changes. The activation of signaling pathways during IRI results in the up- and downregulation of genes and microRNAs (miRNAs). miRNAs are ~21 nucleotides in length and well-characterized for their role in gene regulations; they have recently been used for therapeutic approaches in addition to their role as biomarkers for many diseases. miRNAs that are associated with hepatic IRI in in vitro and in vivo animal models are comprehensively summarized in this review. In those studies, the manipulation of miRNAs has been shown for the inhibition of aggravated immune response, reduction of apoptosis, stimulation of tissue repair, and enhancement of cell recovery to attenuate liver damage. Therefore, the utilization of liver-specific miRNA holds great potential as a therapeutic agent to improve early allograft dysfunction, hepatic injury, and patient outcome.

摘要

肝缺血再灌注损伤(IRI)是早期移植物功能障碍(EAD)的主要因素之一,这可能导致肝移植中的移植物排斥、移植物丢失或移植物寿命缩短。在大多数供体器官的肝脏获取和运输过程中,肝IRI似乎不可避免,从而导致一系列生物学变化。IRI期间信号通路的激活导致基因和微小RNA(miRNA)的上调和下调。miRNA长度约为21个核苷酸,因其在基因调控中的作用而被充分表征;除了作为许多疾病的生物标志物外,它们最近还被用于治疗方法。本综述全面总结了在体外和体内动物模型中与肝IRI相关的miRNA。在这些研究中,已表明对miRNA的操纵可抑制加剧的免疫反应、减少细胞凋亡、刺激组织修复以及增强细胞恢复以减轻肝损伤。因此,利用肝脏特异性miRNA作为治疗剂来改善早期移植物功能障碍、肝损伤和患者预后具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b87c/9028838/067120db29af/biomedicines-10-00791-g001.jpg

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