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杨玉琴,徐春华,周文江,周晓辉.两种呼吸道感染方式建立小鼠流感病毒感染模型的比较[J].中国实验动物学报,2020,28(6):773~778.
两种呼吸道感染方式建立小鼠流感病毒感染模型的比较
Comparison of mouse models of influenza virus infection established with two respiratory tract infection modes
投稿时间:2020-05-20  
DOI:10. 3969 / j.issn.1005-4847. 2020. 06. 006
中文关键词:  气溶胶  滴鼻  流感病毒  小鼠模型
英文关键词:aerosol  intranasal  influenza virus  mouse model
基金项目:
作者单位E-mail
杨玉琴 上海市第一人民医院,上海 200080 fudanyan2007@ sina.com 
徐春华 上海市公共卫生临床中心,上海 201508  
周文江 复旦大学药学院,上海 201203  
周晓辉 上海市公共卫生临床中心,上海 201508 zhouxiaohui@ shphc.org.cn 
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中文摘要:
       目的 探讨通过两种不同呼吸道感染方式建立小鼠流感病毒感染模型的差异,为流感病毒发病机制的研究及疫苗和药物的开发选择合适的动物感染模型提供参考。 方法 选用 A/ Puerto Rico / 8 / 34(H1N1)病毒株,分别采用滴鼻和气溶胶的方法感染 C57BL/ 6 小鼠,每日称小鼠体重,肉眼观察小鼠临床症状,并于感染后 3、7、 14 d 处死小鼠,取肺称其湿重并进行病毒检测、病理观察及肺内细胞因子的测定。 结果 两种感染方式均可成功建立流感病毒小鼠模型,病程进展的总体趋势基本一致,但两组小鼠流感模型的感染特点存在一定差异。气溶胶感染组与滴鼻感染组相比,体重降低出现较早,在感染后第 3 天肺指数、病毒载量明显升高(P< 0. 05),病变范围和炎症细胞因子的浸润程度也明显增加;肺内 IL-1α、IL-6 细胞因子水平在感染后第 3、7 天明显升高(P< 0. 05), TNF-α在感染后第 7 天明显升高(P< 0. 05)。 结论 两种感染方式均可建立小鼠流感模型,经气溶胶感染方式建立的模型在感染早期就可以引起肺部明显的炎症浸润及细胞因子表达,是一种较为理想的流感病毒感染动物模型。
英文摘要:
       Objective To explore the differences in modeling influenza virus infection with two different respiratory tract infection modes in mice; and provide a reference for choosing the appropriate infection model for pathogenic research on influenza and developing vaccines and drugs. Methods The A/ Puerto Rico / 8 / 34 (H1N1) virus strain was selected to infect C57BL/ 6 mice by intranasal instillation and aerosol inhalation. The mice were weighed daily and their clinical symptoms were observed visually. Mice were killed on the 3rd, 7th, or 14th day after infection, and the lungs were weighed and used for virus assay, pathological observation and cytokine detection. Results Both infection modes successfully established an influenza virus infection model in a mouse, and their general trends of disease progression were similar. However, there are some differences in infection characteristics between the two models. Compared with the intranasal instillation group, weight loss occurred earlier in the aerosol inhalation group, and the lung index and viral load increased significantly on the 3rd day after infection (P< 0. 05). The lesion range and degree of inflammatory cytokine infiltration were also significantly increased in the aerosol group. Furthermore, the levels of cytokines interleukin( IL) -1α and IL-6 in the lung increased significantly on the 3rd and 7th days after infection, and tumor necrosis factor-α increased significantly on the 7th day (P< 0. 05). Conclusions Both modes of infection established a model of influenza in the mouse,but aerosol inhalation caused more obvious inflammatory infiltration and cytokine expression in the lung at an early stage of infection. The aerosol inhalation mode led to a more ideal animal model of influenza virus infection.
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