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肺部炎症的机制性理解:最新进展与新兴技术

Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.

作者信息

Keskinidou Chrysi, Vassiliou Alice G, Dimopoulou Ioanna, Kotanidou Anastasia, Orfanos Stylianos E

机构信息

First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, "Evangelismos" Hospital, Athens, Greece.

出版信息

J Inflamm Res. 2022 Jun 15;15:3501-3546. doi: 10.2147/JIR.S282695. eCollection 2022.

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by an acute inflammatory response in the lung parenchyma. Hence, it is considered as the most appropriate clinical syndrome to study pathogenic mechanisms of lung inflammation. ARDS is associated with increased morbidity and mortality in the intensive care unit (ICU), while no effective pharmacological treatment exists. It is very important therefore to fully characterize the underlying pathobiology and the related mechanisms, in order to develop novel therapeutic approaches. In vivo and in vitro models are important pre-clinical tools in biological and medical research in the mechanistic and pathological understanding of the majority of diseases. In this review, we will present data from selected experimental models of lung injury/acute lung inflammation, which have been based on clinical disorders that can lead to the development of ARDS and related inflammatory lung processes in humans, including ventilation-induced lung injury (VILI), sepsis, ischemia/reperfusion, smoke, acid aspiration, radiation, transfusion-related acute lung injury (TRALI), influenza, (.) and coronaviruses infection. Data from the corresponding clinical conditions will also be presented. The mechanisms related to lung inflammation that will be covered are oxidative stress, neutrophil extracellular traps, mitogen-activated protein kinase (MAPK) pathways, surfactant, and water and ion channels. Finally, we will present a brief overview of emerging techniques in the field of omics research that have been applied to ARDS research, encompassing genomics, transcriptomics, proteomics, and metabolomics, which may recognize factors to help stratify ICU patients at risk, predict their prognosis, and possibly, serve as more specific therapeutic targets.

摘要

急性呼吸窘迫综合征(ARDS)是一种危及生命的肺损伤,其特征是肺实质发生急性炎症反应。因此,它被认为是研究肺部炎症致病机制最合适的临床综合征。ARDS与重症监护病房(ICU)中发病率和死亡率的增加相关,而目前尚无有效的药物治疗方法。因此,充分阐明其潜在的病理生物学和相关机制,以开发新的治疗方法非常重要。体内和体外模型是生物学和医学研究中重要的临床前工具,有助于从机制和病理方面理解大多数疾病。在本综述中,我们将展示从选定的肺损伤/急性肺部炎症实验模型中获得的数据,这些模型基于可导致人类发生ARDS及相关肺部炎症过程的临床病症,包括机械通气诱导的肺损伤(VILI)、脓毒症、缺血/再灌注、烟雾吸入、酸误吸、辐射、输血相关急性肺损伤(TRALI)、流感、(.)以及冠状病毒感染。我们还将展示相应临床病症的数据。所涵盖的与肺部炎症相关的机制包括氧化应激、中性粒细胞胞外陷阱、丝裂原活化蛋白激酶(MAPK)信号通路、表面活性剂以及水和离子通道。最后,我们将简要概述已应用于ARDS研究的组学研究领域的新兴技术,包括基因组学、转录组学、蛋白质组学和代谢组学,这些技术可能识别有助于对ICU中高危患者进行分层、预测其预后并可能作为更具特异性治疗靶点的因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45a7/9207257/2ce2363c2c61/JIR-15-3501-g0001.jpg

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