诱导严重急性肺损伤的小鼠模型的适用性。

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pulmonary pharmacology & therapeutics Pub Date : 2024-07-26 DOI:10.1016/j.pupt.2024.102316
Ana Paula Ferreira Leal , Valentina Nieto Marín , Vinícius Varzim Cabistany , Júlia Morales , Danieli Fernanda Buccini , Octávio Luiz Franco
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引用次数: 0

摘要

急性肺损伤(ALI)是与高发病率和高死亡率相关的重大临床挑战。全世界每年约有 20 万人受到急性肺损伤的影响,住院病例的死亡率高达 40%,院外病例的并发症持续存在。本综述将重点关注细菌性急性呼吸道感染的关键免疫学途径,以及将小鼠模型作为诱导工具的探索。这些模型是揭示 ALI 所固有的炎症级联和生物反应不可或缺的平台,同时也有助于评估新型治疗药物。然而,它们的应用并非没有挑战,这主要是由于不同细菌的毒力特征要求严格的生物安全协议。目前已有简单、可重复的肺部细菌感染模型,包括气管内、鼻内、胸膜和腹膜内方法。这些模型使用市售的脂多糖(LPS)等内毒素或铜绿假单胞菌、结核分枝杆菌和肺炎链球菌等活病原体,所有这些病原体都与 ALI 的发病机制有关。将细菌性肺部感染的小鼠模型与对潜在免疫机制的深入研究相结合,是推动急性细菌性肺损伤治疗前景的基石。
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Applicability of mouse models for induction of severe acute lung injury

Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Streptococcus pneumoniae, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.

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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
41
审稿时长
42 days
期刊介绍: Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.
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