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缺氧肾脏:发病机制及基于非编码RNA的治疗策略

The hypoxic kidney: pathogenesis and noncoding RNA-based therapeutic strategies.

作者信息

Haddad George, Kölling Malte, Lorenzen Johan M

机构信息

Division of Nephrology, University Hospital Zurich, Switzerland.

出版信息

Swiss Med Wkly. 2019 Jan 13;149:w14703. doi: 10.4414/smw.2019.14703. eCollection 2019 Jan 1.

DOI:10.4414/smw.2019.14703
PMID:30636273
Abstract

Acute kidney injury (AKI) is a disease entity of major importance, affecting approximately 6% of all patients on the intensive care unit. The mortality rate exceeds 60%. AKI is related to several underlying conditions, including sepsis, nephrotoxicity or major surgery. Ischaemia reperfusion injury or hypoxic conditions may lead to severe injury of the kidney and is associated with a steep decline in survival rates of patients. At present, AKI is diagnosed on the basis of creatinine levels and urine output. Novel markers and knowledge of their pathophysiological role is of major importance for targeted therapeutic interventions. Noncoding RNAs (ncRNAs) have recently been introduced and are the subject of intensive research initiatives. They are arbitrarily separated into small ncRNAs (≤200 nucleotides) and long ncRNAs (lncRNAs, ≥200 nucleotides). Whereas small ncRNAs such as microRNAs have been extensively studied over the past several years, investigations into the role of linear lncRNAs and circular RNAs (circRNAs) are largely lacking. The present review article therefore aims to elucidate in detail the role of microRNAs, lncRNAs and circRNAs in animal models as well as patients with ischaemic AKI and to describe their use as biomarkers as well as their potential use as therapeutics.

摘要

急性肾损伤(AKI)是一种极为重要的疾病实体,影响着重症监护病房中约6%的患者。死亡率超过60%。AKI与多种潜在病症相关,包括脓毒症、肾毒性或大手术。缺血再灌注损伤或缺氧状况可能导致肾脏严重损伤,并与患者生存率的急剧下降相关。目前,AKI是根据肌酐水平和尿量来诊断的。新型标志物及其病理生理作用的知识对于靶向治疗干预至关重要。非编码RNA(ncRNAs)最近被引入,并且是密集研究计划的主题。它们被任意分为小ncRNAs(≤200个核苷酸)和长ncRNAs(lncRNAs,≥200个核苷酸)。尽管诸如微小RNA等小ncRNAs在过去几年中已被广泛研究,但对线性lncRNAs和环状RNA(circRNAs)作用的研究在很大程度上仍很缺乏。因此,本综述文章旨在详细阐明微小RNA、lncRNAs和circRNAs在动物模型以及缺血性AKI患者中的作用,并描述它们作为生物标志物的用途以及作为治疗药物的潜在用途。

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