Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice
Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice
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DOI：
10.1164/rccm.200511-1751oc
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发表时间：
2006-11-01
影响因子：
24.7
通讯作者：
Dong, Changgui
中科院分区：
文献类型：
--
作者：
Xu, Tong;Qiao, Jian;Dong, Changgui
理由和目的：自1997年在香港发现H5 N1禽流感病毒感染人类以来，已报道了许多人感染H5 N1禽流感病毒引起的急性呼吸窘迫综合征（ARDS），但文献中尚未发现关于H5 N1病毒感染ARDS动物模型的研究。方法：将1 × 10（2）50%小鼠感染剂量的A/Chicken/ Hebei/108/2002（H5 N1）病毒经鼻内接种6 ~ 8周龄BALB/c小鼠，建立H5 N1病毒致小鼠ARDS模型。通过观察肺含水量和组织病理学改变评价肺损伤。在指定时间点检测动脉血气、支气管肺泡灌洗液中的白色细胞计数、支气管肺泡灌洗液和血清中的肿瘤坏死因子-α和白细胞介素-6。（1）约80%的小鼠（13/16）在接种后第6 - 8天死亡;（2）肺高度水肿，肺湿重：干重比和肺湿重：体重比显著增加;（3）炎性细胞浸润、肺泡和间质水肿以及肺出血;（4）进行性和重度低氧血症;（5）BALF中中性粒细胞、肿瘤坏死因子-α和白细胞介素-6水平显著升高。结论：成功建立了H5 N1病毒感染的小鼠ARDS模型，为进一步研究H5 N1病毒致人ARDS的发病机制奠定了基础。
Rationale and Objective: The acute respiratory distress syndrome (ARDS) caused by avian influenza H5N1 viral infection has been reported in many humans since this virus was found to infect humans in Hong Kong in 1997, but no studies regarding an animal model of ARDS with H5N1 viral infection have been found in the literature. Here we present a mouse model of ARDS induced by H5N1 virus.Methods: Six- to 8-wk-old BALB/c mice were inoculated intranasally (50 mu l) with 1 X 10(2) 50% mouse infectious doses of A/Chicken/ Hebei/108/2002 (H5N1) virus. Lung injury was assessed by observation of lung water content and histopathology. Arterial blood gas, white blood cell count in bronchial alveolar lavage fluid, and tumor necrosis factor-alpha and interleukin-6 in bronchoalveolar lavage fluid and serum were measured at the indicated time points.Results: Our data showed that H5N1 viral infection in mice resulted in typical ARDS, which was characterized by the following features: (1) about 80% of mice (13 of 16) dead on Days 6 to 8 postinoculation; (2) highly edematous lungs and dramatically increased lung wet:dry weight ratios and lung wet weight:body weight ratios; (3) inflammatory cellular infiltration, alveolar and interstitial edema, and hemorrhage in lungs; (4) progressive and severe hypoxemia; and (5) significant increase in neutrophils, tumor necrosis factor-alpha, and interleukin-6 in BALF.Conclusion: These results suggested that we successfully established a mouse model of ARDS with H5N1 viral infection, which may benefit further investigation into the pathogenesis of human ARDS induced by H5N1 virus.