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用于研究侵袭性肺曲霉病中菌丝发育的鼠模型。

Murine model to follow hyphal development in invasive pulmonary aspergillosis.

机构信息

Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, 1 Egyetem Square, Debrecen, H-4002, Hungary.

Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4002, Hungary.

出版信息

Appl Microbiol Biotechnol. 2018 Mar;102(6):2817-2825. doi: 10.1007/s00253-018-8800-4. Epub 2018 Feb 8.

DOI:10.1007/s00253-018-8800-4
PMID:29423632
Abstract

Aspergillus fumigatus is an opportunistic pathogen, the leading cause of invasive and disseminated aspergillosis in systemic immunocompromised patients, and an important cause of mortality. The aim of the present study was to adapt a pulmonary aspergillosis murine model, to determine pathodynamical parameters quantitatively, and to follow the progression of fungal infection in vivo. The nasal inoculation of Aspergillus conidia in mice previously subjected to immunosuppression with cyclophosphamide (CP) turned out to be a more suitable model than that of immunosuppressed with hydrocortisone (HC). The following parameters were found to correlate quantitatively with the progress of the infection: (i) survival rate, (ii) weight loss of mice, (iii) infected focal plaque size, (iv) hyphal density, (v) hyphal length distribution of A. fumigatus, and the (vi) the histopathological status and scores. These parameters will be essential elements for the development of antifungal drugs and therapies, and important for the investigation of the pathogenicity in different strains of A. fumigatus.

摘要

烟曲霉是一种机会性病原体,是导致系统性免疫功能低下患者侵袭性和播散性曲霉病的主要原因,也是导致死亡率的重要原因。本研究旨在适应一种肺部曲霉病的小鼠模型,对其进行定量的病理动力学参数检测,并在体内跟踪真菌感染的进展情况。与用氢化可的松(HC)进行免疫抑制的模型相比,用环磷酰胺(CP)预先对小鼠进行免疫抑制后的烟曲霉孢子鼻腔接种是一种更合适的模型。研究发现以下参数与感染的进展呈定量相关:(i)存活率,(ii)小鼠体重减轻,(iii)感染灶斑块大小,(iv)菌丝密度,(v)烟曲霉菌丝长度分布,以及(vi)组织病理学状态和评分。这些参数将是开发抗真菌药物和疗法的重要元素,对于研究不同烟曲霉菌株的致病性也非常重要。

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