重症甲型H1N1流感八例呼吸系统病理学特征分析

Pulmonary pathology in fatal human influenza A （H1N1） infection

目的 探讨重症甲型H1N1流感死亡患者呼吸系统病理变化特征.方法 收集北京市8例重症甲型H1N1流感死亡病例,其中6例为死后床旁穿刺标本,2例为系统尸体解剖标本,进行常规病理形态学观察,并利用免疫组织化学、流式细胞术、Western blot等技术进行病毒定位检测.结果 重症甲型H1N1流感患者呼吸系统的主要病理改变为坏死性支气管炎伴周围炎、弥漫性肺泡损伤、肺出血.Westem blot检测肺组织内可见病毒抗原的表达,免疫组织化学染色显示甲型H1N1病毒核蛋白、血凝素抗原主要表达于部分气管、细支气管上皮及腺体、肺泡上皮细胞、巨噬细胞、血管内皮细胞等.流式细胞术检测2例尸体解剖病例肺内Ⅱ型肺泡上皮凋亡率（32.15％,78.15％）明显高于对照组（1.93％,3.77％）.结论 弥漫性肺泡损伤、肺出血和晚期的肺纤维化是甲型H1N1流感重症死亡的主要病理改变；肺脏的损伤可能与病毒侵袭有关.

Objective To study the pulmonary pathology in patients died of fatal human influenza A（H1N1） infection.Methods Eight cases of fatal human influenza A （H1N1） infection,including 2 autopsy cases and 6 paramortem needle puncture biopsies,were enrolled into the study.Histologic examination,immunohistochemitry,flow cytometry and Western blotting were carried out.Results The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation,diffuse alveolar damage and pulmonary hemorrhage.Influenza viral antigen expression was detected in the lung tisue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea,bronchial epithelium and glands,alveolar epithelium,macrophages and endothelium.Flow cytometry showed that the apoptotic rate of type Ⅱ pneumocytes （32.15%,78.15% ） was significantly higher than that of the controls （ 1.93%,3.77% ）.Conclusion Necrotizing bronchiolitis,diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A （H1N1） infection.