A multiple comorbidities mouse lung infection model in ApoE‑deficient mice.

IF 2.3 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Biomedical reports Pub Date : 2023-02-06 eCollection Date: 2023-03-01 DOI:10.3892/br.2023.1603
Benjamin Bartlett, Silvia Lee, Herbert P Ludewick, Teck Siew, Shipra Verma, Grant Waterer, Vicente F Corrales-Medina, Girish Dwivedi
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引用次数: 0

Abstract

Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE -/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1β and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.

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载脂蛋白E缺陷小鼠肺部感染模型的多种合并症。
急性肺炎的特点是炎症反应剧烈。目前,炎症被认为是动脉粥样硬化进展的关键步骤。此外,已有的动脉粥样硬化性炎症也被认为在肺炎的进展和风险中起着一定的作用。在本研究中,我们使用了一种多种合并症的小鼠模型来研究动脉粥样硬化情况下肺炎导致的呼吸道和全身炎症。首先,建立了一个最小感染剂量的肺炎链球菌(TIGR4 株)模型,以产生低死亡率(20%)的临床肺炎。在给 C57Bl/6 ApoE -/- 小鼠鼻内注射 105 个菌落形成单位的 TIGR4 或磷酸盐缓冲盐水(PBS)之前,先喂食高脂肪食物。在接种后第 2、7 和 28 天(PI),通过磁共振成像(MRI)和正电子发射断层扫描(PET)对小鼠的肺部进行成像。小鼠安乐死后,使用 ELISA、Luminex 检测法和实时 PCR 检测肺部形态变化和全身炎症变化。TIGR4接种的小鼠在PI 28天内的所有时间点上都出现了不同程度的肺部浸润、胸腔积液和核磁共振成像上的合并症。此外,正电子发射计算机断层扫描发现,TIGR4 接种小鼠肺部的 FDG 摄取量明显较高,一直持续到发病前 28 天。大多数(90%)接种 TIGR4 的小鼠在发病前 28 天出现了肺炎球菌特异性 IgG 抗体反应。与这些观察结果一致的是,TIGR4 接种小鼠的肺部炎症基因表达[白细胞介素 (IL)-1β 和 IL-6]明显增加,循环炎症蛋白 (CCL3) 水平也分别在发病前 7 天和发病前 28 天明显增加。作者开发的小鼠模型为了解肺炎等急性感染相关炎症与人类心血管疾病风险增加之间的联系提供了一种发现工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical reports
Biomedical reports MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
4.10
自引率
0.00%
发文量
86
期刊介绍: Biomedical Reports is a monthly, peer-reviewed journal, dedicated to publishing research across all fields of biology and medicine, including pharmacology, pathology, gene therapy, genetics, microbiology, neurosciences, infectious diseases, molecular cardiology and molecular surgery. The journal provides a home for original research, case reports and review articles.
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