Pulmonary fibrosis induced by H5N1 viral infection in mice.

Pulmonary fibrosis induced by H5N1 viral infection in mice.
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DOI:
10.1186/1465-9921-10-107
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发表时间:
2009-11-12
影响因子:
5.8
通讯作者:
Zhao L
Zhao L
中科院分区:
医学2区
文献类型:
--
作者:
Qiao J;Zhang M;Bi J;Wang X;Deng G;He G;Luan Z;Lv N;Xu T;Zhao L

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炎症过程导致肺损伤,可能导致肺纤维化(PF)。在这里,我们描述了PF感染H5 N1病毒的小鼠。8周龄BALB/c小鼠鼻内接种1 × 101 MID 50的A/Chicken/Hebei/108/2002(H5 N1)病毒。通过观察接种后第7、14和30天的羟脯氨酸浓度、肺指数和组织病理学来评价肺损伤/纤维化。接种H5 N1病毒的小鼠在感染后30天内出现了两个阶段的肺部疾病。急性期,感染小鼠于接种后第7天出现典型的弥漫性肺炎,伴有炎性细胞浸润、肺泡和间质水肿和出血。在恢复期,大多数感染小鼠在接种后30天发生不同程度的PF,18%的存活小鼠发生严重的肺泡间质和肺泡内纤维化,肺泡壁增厚,肺泡塌陷和大面积纤维化。H5 N1感染小鼠的羟脯氨酸水平显著升高,表明肺中胶原沉积,并证实肺纤维化。H5 N1感染组小鼠的肺干重/体重比显著增加,这可能与H5 N1感染小鼠肺纤维化的形成有关。我们的研究结果表明,H5 N1感染的小鼠在恢复期出现了典型的PF,这将有助于研究人类H5 N1疾病的纤维化和潜在的治疗干预。
Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus. Eight-week-old BALB/c mice were inoculated intranasally with 1 × 101 MID50 of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation. H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice. Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.
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