BALB/c小鼠多重耐药鲍曼不动杆菌肺部感染模型的建立和评估

柴媛1,王俊瑞2,英兰3,王继春4,朝鲁门其其格1

微生物与感染 ›› 2022, Vol. 17 ›› Issue (2) : 71-80.

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微生物与感染 ›› 2022, Vol. 17 ›› Issue (2) : 71-80. DOI: 10.3969/j.issn.1673-6184.2022.02.002
论著

BALB/c小鼠多重耐药鲍曼不动杆菌肺部感染模型的建立和评估

  • 柴媛1,王俊瑞2,英兰3,王继春4,朝鲁门其其格1
作者信息 +

Establishment and evaluation of a BALB/c mouse model of pulmonary multidrug-resistant Acinetobacter baumannii infection

  • CHAI Yuan1, WANG Junrui2, YING Lan3, WANG Jichun4, Chaolumenqiqige1
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摘要

本研究旨在构建小鼠多重耐药鲍曼不动杆菌肺部感染模型,评估模型小鼠各项炎性指标的变化特征,为研究多重耐药鲍曼不动杆菌的体内致病性提供参考。首先采用聚合酶链反应(polymerase chain reaction,PCR)检测拟建模用鲍曼不动杆菌的毒力基因分布特征,然后通过感染秀丽隐杆线虫筛选建模菌株。结果显示,A5株携带更多的毒力基因,致病性也更强,被选为建模菌株。给小鼠注射环磷酰胺建立免疫抑制,雾化吸入A5株菌液(高、低密度组),监测小鼠状态、肺组织改变、肺组织和肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中菌落计数、外周血白细胞和中性粒细胞计数、细胞因子等的变化。结果显示,感染A5株的小鼠较对照组状态更差,肺充血水肿,肺组织和BALF中出现鲍曼不动杆菌增殖。与低密度组相比,高密度组小鼠外周血白细胞和中性粒细胞增加更明显(白细胞F=78.630,P=0.000;中性粒细胞:F=4.762,P=0.053)。与对照组相比,感染A5株的小鼠血清白细胞介素6(interleukin 6,IL-6)水平升高并趋于稳定(F=14.382, P=0.001),而肿瘤坏死因子α(tumor necrosis factor α,TNF-α)水平持续升高(F=4.558,P=0.032),高密度组与低密度组TNF-α变化趋势不完全一致。结果提示,本研究成功构建了小鼠多重耐药鲍曼不动杆菌肺部感染模型,且模型小鼠出现了明显的感染症状,接种菌量与小鼠感染程度呈正相关。

Abstract

The purpose of this study is to construct a mouse model of pulmonary infection by multidrug-resistant Acinetobacter baumannii (A. baumannii), and to evaluate the changes in various inflammatory indicators in the model mice, so as to provide a reference for studying the pathogenicity of multidrug-resistant A. baumannii in vivo. First of all, polymerase chain reaction (PCR) was used to detect the distribution characteristics of virulence genes of A. baumannii. And then, Caenorhabditis elegans was infected with different A. baumannii strains for screening the strain used in modeling. The results demonstrated that strain A5 not only carried more virulence genes, but also had stronger pathogenicity. Immunosuppression was induced by injection of cyclophosphamide in mice. Selected strain A5 solution (high and low density) was inhaled by nebulization in immunosuppressive mice. The health state, lung tissue changes, colony counts in lung tissues and bronchoalveolar lavage fluid (BALF), peripheral blood leukocyte and neutrophil counts, and cytokine changes in mice were monitored. Compared with the control group, the mice infected with strain A5 showed significantly worse state, pulmonary hyperemia and edema. Meanwhile, A. baumannii showed proliferation in the lungs and BALF of mice. The number of peripheral leukocytes and neutrophils in the high density group increased more obviously than that in the low density group (Leukocyte: F=78.630, P=0.000; Neutrophil: F=4.762, P=0.053). Compared with the control group, the level of interleukin 6 (IL-6) in the mice infected with A5 strain was higher and tended to be stable (F=14.382, P=0.001), but the level of tumor necrosis factor α (TNF-α) kept increasing (F=4.558, P=0.032). Moreover, the variation trend of TNF-α between high and low density groups was not completely consistent. In this study, a mouse model of pulmonary multidrug-resistant A. baumannii infection is successfully constructed. The model mice shows obvious symptoms of infection, and A. baumannii load is positively correlated with the degree of infection in the mice.

关键词

多重耐药鲍曼不动杆菌 / 动物模型 / 肺部感染

Key words

Multidrug-resistant Acinetobacter baumannii / Animal model / Pulmonary infection

引用本文

导出引用
柴媛1,王俊瑞2,英兰3,王继春4,朝鲁门其其格1. BALB/c小鼠多重耐药鲍曼不动杆菌肺部感染模型的建立和评估[J]. 微生物与感染. 2022, 17(2): 71-80 https://doi.org/10.3969/j.issn.1673-6184.2022.02.002
CHAI Yuan1, WANG Junrui2, YING Lan3, WANG Jichun4, Chaolumenqiqige1. Establishment and evaluation of a BALB/c mouse model of pulmonary multidrug-resistant Acinetobacter baumannii infection[J]. Journal of Microbes and Infections. 2022, 17(2): 71-80 https://doi.org/10.3969/j.issn.1673-6184.2022.02.002
中图分类号: R378   

基金

内蒙古自治区蒙医药协同创新科研项目(MYYXTYB202109);内蒙古自治区引智成果示范推广项目(YS2019150005);内蒙古自然科学基金项目(2017MS0847、2020MS08113)

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