BALB/c小鼠和雪貂感染H7N9禽流感病毒后的肺组织动态病理学变化  

Pathological changes of the lungs in mouse and ferret models infected with novel avian-origin human A(H7N9) influenza virus

作　　者：邓巍[1] 李彦红[1] 朱华[1] 徐艳峰[1] 陈霆[1] 李枫棣[1] 鲍琳琳[1] 许黎黎[1] 黄澜[1] 吕琦[1] 袁静[1] 向志光[1] 高凯[1] 姚艳丰[1] 于品[1] 秦川[1] 

机构地区：[1]中国医学科学院北京协和医学院医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京100021

出　　处：《中国实验动物学报》2014年第1期13-17,I0006-I0007,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：科技部应急专项(项目号KJYJ-2013-01-04);国家科技重大专项(项目号2012ZX10004-404,2012ZX10004-501)

摘　　要：目的 了解用H7N9禽流感病毒分别感染BALB/c小鼠和雪貂后,其肺部动态病理改变,为临床诊断、治疗、预防及机制研究提供帮助.方法 BALB/c小鼠经鼻腔接种106EID50（50 μL）H7N9禽流感病毒后第1、2、3、5、7、14、28天分别安乐死2～3只小鼠;雪貂经鼻腔吸入接种106EID50（500 μL）H7N9禽流感病毒后第3、7、14、28天分别安乐死1只雪貂,分别观察动物的临床特征改变,肺组织的大体组织形态学变化,HE染色观察动态病理改变,免疫组化染色观察病毒分布及肺组织各种炎细胞的浸润情况.结果 感染病毒后的小鼠出现竖毛、嗜睡、死亡等表现,雪貂表现为打喷嚏、鼻腔分泌物、稀便、嗜睡等;大体观察小鼠与雪貂肺组织均可见到暗红色病灶;光镜观察小鼠与雪貂的肺组织均呈现坏死性支气管炎和渗出性间质性肺炎、肺泡炎.感染第2天开始出现炎性病变,7～9 d炎症病变最严重,14 d后逐渐修复吸收,28 d基本完全吸收; T、B淋巴细胞,巨噬细胞不同程度的表达增多,以T细胞增多为主,尤其是CD8＋ T细胞两种动物均大量表达.结论 H7N9禽流感病毒感染可引起BALB/c小鼠和雪貂肺组织急性支气管炎和肺炎,感染后7～9 d肺部炎症的组织病理学变化最严重,CD8＋T细胞明显增多,14 d后病灶逐渐吸收.该研究可为临床诊断、治疗、预防该病及进行疾病机制研究提供帮助.Objective To better understand the dynamic pathological changes in the lungs of mouse and ferret models infected with novel avian-origin H7N9 subtype influenza virus. Methods A/Anhui/1/2013 （H7N9） virus was inoculated by intranasal instillation to mice and ferrets. Autopsies of 2-3 mice each time were performed on days 1, 2, 3, 5, 7, 14 and 28 post inoculation （d.p.i.） and 1 ferret on 3, 7, 14 and 28 d.p.i. Clinical signs and gross examination were conducted and histopathological analysis was performed. Results Animals developed typical clinical signs including body weight loss （mice and ferrets）, ruffled fur （mice）, sneezing （ferrets）, diarrhea（ferrets）and death （mice）. Focal infection observed by gross examination and bronchitis and pneumonia determined by histology were seen in the lung in the mouse and ferret models. Inflammatory reaction was started from 2 d.p.i., most severe on 7-9 d.p.i. and absorbed from 14 to 28 d.p.i.. Lymphocytes and macrophages, especially CD8＋ lymphocytes were increased in the lungs of infected mouse and ferret models. Conclusions Bronchitis and pneumonia can be induced in mice and ferrets inoculated with H7N9 virus. Inflammatory reactions are most severe on 7-9 d.p.i. and absorbed from 14 d.p.i., and infiltration of CD8＋ lymphocytes is evident. Observation of pathological changes of the lungs in mouse and ferrets models enables detailed studies of the pathogenesis, diagnosis, treatment and prevention of this illness, and lays foundation for related drug or vaccine evaluation.

关 键 词：H7N9禽流感病毒 BALB C小鼠 雪貂 肺组织 病理学变化 

分 类 号：Q95-33[生物学—动物学]