Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Immunol. 2021 Jul;135:127-136. doi: 10.1016/j.molimm.2021.04.007. Epub 2021 Apr 22.
Mechanical ventilation (MV) is a relatively common medical intervention in ICU patients. The main side effect of MV is the so-called "ventilator-induced lung injury" (VILI). The pathogenesis of VILI is not completely understood; however, it has been reported that MV might be associated with up-regulation of various inflammatory mediators within the lung tissue and that these mediators might act as pathogenic factors in lung tissue injury. One potential mechanism for the generation of inflammatory mediators is through the release of endogenous molecules known as damage associated molecular patterns (DAMPs). These molecules are released from injured tissues and can bind to pattern recognition receptors (PRRs). PRR activation generally leads to the production and release of inflammation-related molecules including innate immune cytokines and chemokines. It has been suggested that blocking DAMP/PRR signaling pathways might diminish the progression of VILI. Herein, we review the latest findings with regard to the effects of DAMP/PRRs and their blockade, as well as the potential therapeutic targets and future research directions in VILI. Results of studies performed on human samples, animal models of disease, as well as relevant in vitro systems will be discussed.
机械通气（MV）是 ICU 患者中较为常见的一种医疗干预措施。MV 的主要副作用是所谓的“呼吸机相关性肺损伤”（VILI）。VILI 的发病机制尚不完全清楚；然而，据报道，MV 可能与肺组织中各种炎症介质的上调有关，这些介质可能作为肺组织损伤的致病因素。炎症介质产生的一个潜在机制是通过释放称为损伤相关分子模式（DAMPs）的内源性分子。这些分子从受损组织中释放出来，并可以与模式识别受体（PRRs）结合。PRR 的激活通常会导致炎症相关分子的产生和释放，包括先天免疫细胞因子和趋化因子。有研究表明，阻断 DAMPs/PRRs 信号通路可能会减缓 VILI 的进展。本文综述了 DAMPs/PRRs 及其阻断的最新研究结果，以及 VILI 的潜在治疗靶点和未来研究方向。将讨论在人类样本、疾病动物模型以及相关体外系统中进行的研究结果。
