RSV感染裸鼠模型建立及病理特征分析

发布时间：2018-12-23 08:53

【摘要】：目的建立呼吸道合胞病毒(respiratory syncytial virus,RSV)感染裸鼠模型,在排除T细胞干扰的情况下,观察RSV的复制情况、气道炎症细胞浸润、肺组织损伤及气道高反应性(AHR),为进一步探讨固有免疫在RSV中的致病作用奠定基础。方法6~8周雌性T细胞缺陷裸鼠(Balb/c背景)及正常Balb/c小鼠分为对照组及RSV组,分别滴鼻接种细胞培养上清或RSV A2病毒液,空斑实验检测病毒滴度;灌取支气管肺泡灌洗液并行炎症细胞计数及分类计数;部分小鼠取左肺,HE染色后行组织病理评分;肺功能检测用全身体积描技法;细胞因子检测用ELISA法。结果裸鼠中病毒清除较Balb/c小鼠延迟;RSV在裸鼠及Balb/c小鼠中均引起明显的炎症细胞浸润、肺组织病理损伤及AHR,且至少可持续60 d;RSV感染裸鼠及Balb/c小鼠后,细胞因子呈双相变化,急性期以干扰素升高为主,慢性期以Th2类细胞因子升高为主。结论固有免疫可不依赖于T细胞,独立介导RSV相关急慢性期气道炎症及AHR,提示RSV疫苗或药物的开发应充分考虑固有免疫的作用。
[Abstract]:Objective to establish a nude mouse model of respiratory syncytial virus (respiratory syncytial virus,RSV) infection and observe the replication of RSV, infiltration of airway inflammatory cells, lung injury and airway hyperresponsiveness (AHR), without T cell interference. It lays a foundation for further study of the pathogenicity of innate immunity in RSV. Methods female T-cell deficient nude mice (Balb/c background) and normal Balb/c mice were divided into control group and RSV group at 6 weeks. The supernatant of cell culture or RSV A2 virus solution were inoculated by nasal drip, and the titer of virus was detected by plaque test. Bronchoalveolar lavage fluid (BALF) was perfused with inflammatory cell count and classified count; some mice took left lung and HE staining was used for histological grading; lung function was measured by whole body sketching technique; cytokine was detected by ELISA method. Results the clearance of virus in nude mice was delayed than that in Balb/c mice, and RSV caused obvious inflammatory cell infiltration in both nude mice and Balb/c mice, and the pathological injury of lung tissue and AHR, could be sustained for at least 60 days. After RSV infection in nude mice and Balb/c mice, cytokines showed a biphasic change. In acute phase, interferon was mainly increased, and in chronic phase, Th2 cytokines were mainly increased. Conclusion innate immunity is independent of T cells and independent mediates acute and chronic airway inflammation associated with RSV and AHR, suggests that the role of innate immunity should be fully considered in the development of RSV vaccine or drug.
【作者单位】：重庆医科大学儿童发育疾病研究教育部重点实验室儿科学重庆市重点实验室重庆市儿童发育重大疾病诊治与预防国际科技合作基地;重庆医科大学附属儿童医院呼吸中心一病房;
【基金】：国家自然科学基金(81170010,81470208)
【分类号】：R-332;R725.1

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