人感染高致病性禽流感病毒H5N1的病理学和病原学特点

Histologic and ultrastructural studies of the patient died of highly pathogenic H5N1 avian influenza virus infection in China

目的探讨人感染禽流行性感冒病毒的病理学及病原学特点。方法应用透射电镜、光镜、组织化学和免疫组织化学方法对发生在2003年11月中国内地人禽流感死亡尸检病例1例进行观察研究。行病原体分离培养鉴定、全基因组序列测定和动物致病性观察以确定病原学特点。结果肺部病理改变主要表现为广泛性肺实变，肺出血、肺水肿及坏死。肺泡腔内充满水肿液、多量红细胞、纤维素，细胞碎片，混合较多的巨噬细胞和中性粒细胞及淋巴细胞，并见少数单核和多核巨细胞，伴有透明膜形成。部分肺组织出血坏死显著，肺泡隔坏死崩解。心肌间质水肿，少数淋巴细胞浸润。电镜下A型禽流感病毒样颗粒多为球形，80—120nm，主要以高电子密度核心居中的C型病毒颗粒为多见，也可见到低电子密度核心的A型病毒颗粒。病毒分离及序列分析确定为A型禽流感病毒（H5N1）。结论高致病性A型禽流感病毒感染所致的严重急性病毒性肺炎以广泛性肺实变、肺水肿和显著的出血性坏死性炎症等病理改变为特征。电镜下查见A型禽流感病毒样颗粒。探讨和研究人禽流行性感冒的病理学和病原学特点，为人禽流感临床诊断和治疗方案的选择提供重要的理论依据和病理学基础。

Objective To explore histopathologic and ultrastructural characteristics of human avian influenza （AI） infection and related etiological pathogenesis. Methods Postmortem lung and heart samples were collected from the patient who died of avian influenza virus infection on November 29, 2003 in China. Light and electron microscopy, immunohistochemistry and histochemistry were used to investigate the pathological changes. Results The main pathological findings included extensive pulmonary consolidation, hemorrhage, pulmonary edema and local hemorrhagic infarct. The lamina of alveoli and bronchioles were abundantly filled with protein-rich fluid, erythrocytes, fibrin and cell debris admixed with many neutrophilis, macrophages, lymphocytes and a few of monokaryon and multinuclear giant cells. Hyaline membranes were formed. Local pulmonary tissues were heavily damaged by hemorrhage and necrosis. Alveolar septum was disintegrated. Mesenchymal edema with a few of macrophages infiltration of heart was found. Electron microscopy showed the avian influenza A virus-like particles （type C and type A） of 80 - 120 nm diameter and envelopes in the cytoplasm of pneumocytes and endothelial cells. Conclusions Fatal pneumonia associated with highly pathogenic avian influenza A virus （ H5N1 ） infection leads to extensive pulmonary consolidation, edema and marked hemorrhagic necrosis and inflammation. Electron microscopy can identify avian influenza A virus-like particles. The findings may offer an important theoretical basis for clinical diagnosis and treatment.