恒河猴H5N1禽流感病毒性肺炎模型建立及其发病机制  

Pathogenesis of influenza A(H5N1) virus-induced viral pneumonia in the rhesus macaque

作　　者：黎东明[1] 赖天文[1] 邓少嫦[2] 吴东[1] 张钰[2] 陈敏[1] 吕莹莹[1] 吴斌[1] 

机构地区：[1]广东医学院附属医院呼吸疾病研究所,湛江524001 [2]广东省实验动物监测所

出　　处：《中国人兽共患病学报》2014年第8期806-811,共6页Chinese Journal of Zoonoses

基　　金：广东省科技项目(No.2011B06030026)项目~~

摘　　要：目的：探讨H5N1病毒（AF148678/ACGoose/Guangdong/11961H5N1）感染恒河猴诱发自初期至恢复期过程肺炎的机制。方法以 H5N1病毒液经鼻滴入恒河猴，染毒后第0h、12h、1d、2d、3d、4d、6d、10d、12d和14d采血作血液学和流感特异抗体检测。染毒后第1、3、6、14 d分别剖杀1只恒河猴，取气管支气管淋巴结、肺、心、肝、肾、大脑及小脑进行病毒分离、滴定、病理及免疫组化检测并观察感染后临床表现。结果猴感染后出现发热、呼吸困难，食欲下降等。病毒仅在肺组织复制，主要侵犯下呼吸道的肺泡上皮细胞和肺巨噬细胞。感染后第1～3d引起暂时性的严重肺炎，主要为中性粒细胞浸润；第6 d后逐渐恢复，以巨噬细胞浸润为主；第14 d后以 T 淋巴细胞浸润为主，肺组织呈恢复期状态。结论下呼吸道是H5N1病毒感染主要攻击的对象，这可能是H5N1病毒在人与人之间传递的障碍之一，其发病可能经过病毒侵入、复制阶段及免疫损伤阶段。At present ,the mechanism of highly pathogenic avian influenza H5N1 virus causing human infection or death is still not fully clear .In order to better understand the pathogenesis of the disease ,the rhesus macaques were infected with H5N1 virus （AF148678/ACGoose/Guangdong/11961H5N1） .We analyzed the clinical symptoms ,characteristics of the virus invades body ,pathological changes ,and immune response to discuss the pathogenesis of viral pneumonia induced by H 5N1 virus infection from the early time to the recovery time .The rhesus macaques were infected with H5N1 virus through nasal .Clinical signs were assessed daily ,and major organs and blood were collected for detection of blood routine analysis ,viruses were isola-ted and titrated from organs ,and pathologic and immunohistochemical were also conducted .As a result ,the rhesus macaques in-fected with H5N1 virus experienced fever ,dyspnea ,and anorexia .The respiratory tract was the major target of the virus and the virus could not replicate in organs outside the respiratory tract .Positive staining cells by immunohistochemistry were bronchial epithelial cells and alveolar macrophages .Rhesus macaques experienced temporary severe pneumonia after 1-3 days ,mainly be-cause of neutrophils infiltration ;gradual recovery 6 days later ,mainly with macrophage infiltration ;lung tissue presented recov-ery state after 14 days ,mainly with T lymphocytes infiltration .Finally ,we concluded that the predilection of the H 5N1 virus to infect the lower airway suggests that it may be a limiting factor in human-to-human transmissibility of the H5N1 virus .The pathogenesis may include virus invasion ,replication and immune injury .

关 键 词：H5N1禽流感病毒 恒河猴 非人灵长类动物模型 

分 类 号：R373[医药卫生—病原生物学]