不同致病力禽流感病毒比较研究的适宜小鼠模型筛选

摘要

目的 筛选用于不同致病力禽流感病毒比较研究的适宜小鼠模型.方法 采用禽流感病毒高致病力毒株H7N9和低致病力毒株H9N2分别以滴鼻方式感染C57BL/6和BALB/c小鼠,观察小鼠临床症状、病理变化并检测体内病毒载量.结果 小鼠感染两类禽流感病毒1d后均出现竖毛、聚集成堆、反应迟钝、四肢无力等症状.H7N9与H9N2感染BALB/c小鼠导致的体重丢失最低点分别为63.80％与66.35％,均低于C57BL/6小鼠(分别为68.96％与87.57％).感染小鼠的肺组织都存在间质肺炎、水肿、充血、炎细胞浸润等病理症状,H7N9感染C57BL/6小鼠后肺组织病毒载量峰值(1.02×105拷贝/ml)约为BALB/c组(8.72×103拷贝/ml)12倍;而H9N2感染后C57BL/6小鼠肺组织病毒载量(5.94×103拷贝/ml)仅为BALB/c小鼠(2.86×104拷贝/ml)的20％.结论 C57BL/6小鼠感染禽流感病毒更能表现出强弱毒株的致病特点,更适用于不同致病力禽流感病毒比较研究.小鼠的病理变化与临床特征与接种禽流感病毒株的生物学特征及小鼠品系均密切相关.%Objective To filter appropriate mouse model for avian influenza viruses with different pathogenicity.Methods Two varieties mice (C57BL/6 and BALB/c) were anesthetized with ketamine and inoculated intranasal with highly pathogenic avian influenza virus H7N9 and low pathogenic avian influenza virus H9N2 in 50 μl PBS,or mock inoculated with PBS to serve as controls.The mice were observed daily including clinical symptoms body,weight and mortality.The pulmonary histopathological changes and viral load were also monitored.Results Just one day after the viral inoculation,H7N9 and H9N2 infected mice strains all showed reduced activity,ruffled fur and obvious body weight loss.The body weight loss nadir in BALB/c mice (63.80％ for H7N9/BALB/c;66.35％ for H9N2/BALB/c) were lower comparing to the corresponding viruses infected C57BL/6 mice (68.96％ for H7N9/C57BL/6 and 87.57％ for H9N2/ C57BL/6 respectively).In addition,there were some obvious pulmonary oedema,haemorrhage and typical pulmonary interstitial inflammatory lesions in the lung tissues.The peak viral load in H7N9/C57BL/6 group (1.02 × 105 copies/ml) was 12 folds higher than that in H7N9/BALB/c group (8.7 × 103 copies/ml).But on the contrary,the peak viral load in H9N2/BALB/c group (2.86 × 104 copies/ml) was 5 times of that in H9N2/C57BL/6 group (5.94 × 103 copies/ml).Conclusions Pathogenic characteristics caused by different virulent avian influenza viral strains could be more clearly differential represented in C57BL/6 mice model,and thus it is more suitable for the comparative study between different pathogenic avian influenza viruses.It also reconfirmed that the different pathological changes and clinical outcomes of avian influenza viruses/mice infection models were associated not only to the different biological characteristics of inoculated virus strains,but also to hereditary characters of host mice strains.