严重急性呼吸综合征的临床病理及发病机制研究

目的　研究严重急性呼吸综合征 (SARS)的病理学特征及临床治疗的病理学基础 ,并探讨SARS的发病机制。方法　采用光、电镜观察 ,对 2例SARS系统尸检病例和 4例多器官多部位穿刺标本进行病理学观察 ;应用免疫组化标记并分析肺组织及免疫器官中各淋巴亚群的分布及数量变化 ;核酸原位杂交结合电镜观察 ,作SARS冠状病毒 (SARS CoV)在体病原学定位及定量检测。结果　 6例SARS肺组织均呈弥漫性肺泡上皮损伤 ,2例尸检肺组织呈急性间质性炎和区域性肺水肿 ,2例尸检和1例穿刺肺组织中肺泡腔内透明膜形成 ,1例尸检和 2例穿刺肺组织呈脱屑性终末细支气管炎及肺泡炎 ,2例穿刺病例见早期肺纤维化及肺泡腔机化。SARS肺外器官 ,2例病程 <12dSARS病例免疫器官呈较广泛的出血坏死性炎 ,组织细胞及单核细胞样免疫母细胞反应性增生 ,骨髓组织内单核 粒细胞系统相对抑制 ,而 4例病程 >2 1dSRAS病例脾脏中央动脉周围T淋巴细胞增生 ,骨髓像大致正常。体内SARS CoV存在多种感染靶细胞和靶器官 ,其中肺脏为主要靶器官 ,支气管、肾、肾上腺、心肌、胃肠道、淋巴组织及睾丸等也为靶器官。肺组织内以CD8+ 细胞浸润为主 ,杂以少数CD4 + 细胞 ;淋巴结及脾脏中CD3+ 、CD4 + 、CD8+ 和CD2 0 + 淋巴细胞亚群呈不同程度减少及比例失衡 ,而

Clinical pathology and pathogenesis of severe acute respiratory syndrome

BACKGROUND: To explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS. METHODS: Pathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry. RESULTS: In total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens. CONCLUSIONS: Histologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.