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致命性甲型流感(H1N1)的肺部组织病理学观察结果。

Lung histopathological findings in fatal pandemic influenza A (H1N1).

机构信息

Hospital Universitario de Getafe, Madrid, Spain.

出版信息

Med Intensiva. 2012 Jan-Feb;36(1):24-31. doi: 10.1016/j.medin.2011.10.005. Epub 2011 Dec 10.

DOI:10.1016/j.medin.2011.10.005
PMID:22154847
Abstract

OBJECTIVE

To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue.

METHODS AND PATIENTS

Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens.

RESULTS

Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy.

CONCLUSIONS

Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.

摘要

目的

描述甲型流感(H1N1)病毒性肺炎的肺部病理变化。我们研究了形态学变化、硝化-氧化应激以及肺组织中病毒蛋白的存在。

方法和患者

使用光镜检查了 6 例大流行性甲型流感(H1N1)病毒性肺炎的致死病例的肺组织。还研究了肺组织标本中氧化二氢乙锭、硝基酪氨酸、诱导型一氧化氮合酶(NOS2)和人甲型流感核蛋白(NP)(用于共聚焦显微镜分析)的荧光。

结果

年龄在 15 至 50 岁之间。3 名患者为女性,5 名患者有预先存在的医疗条件。5 例存在弥漫性肺泡损伤(DAD)(表现为透明膜形成、肺泡-毛细血管壁增厚和PMN 浸润),1 例存在间质性纤维化。在荧光研究中,无论 ICU 住院时间长短,肺组织样本中均存在氧自由基生成、NOS2 蛋白增加和蛋白硝化的迹象。从 3 例患者的肺组织样本中发现了病毒 NP。I 型肺泡细胞和巨噬细胞含有病毒 NP,这一点可以通过共聚焦免疫荧光显微镜得到证明。

结论

大流行性甲型流感(H1N1)病毒性肺炎患者的肺组织显示出与 DAD 一致的组织学发现。尽管进行了抗病毒治疗,但仍存在长期的硝化-氧化应激。病毒蛋白可能在肺组织中长时间存在,寄生于巨噬细胞和 I 型肺泡细胞中。

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