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目的为了明确实验性感染SARS-CoV的果子狸各器官的病理变化,进一步确定SARS-CoV与果子狸的关系,评价其作为SARS动物模型的可行性。方法在人源SARS-CoV分离株BJ01(有29个核苷酸的缺失序列)和GD01(无29个核苷酸的缺失序列)实验性感染果子狸的基础上,对其经福尔马林固定的肺、脾、淋巴结、肝、小肠、肾、气管、大脑、胰腺、性腺、胃、心组织进行病理组织学观察,同时用原位杂交技术(ISH)对SARS-CoV在组织器官中的分布进行检测。结果攻毒后不同时期,肺、脾、淋巴结、肝、小肠、肾和大脑有不同程度的病理变化,主要病变是肺脏为急性间质性肺炎:肺炎性水肿、肺泡腔浆液渗出以及肺泡壁充血、出血并因淋巴细胞、巨噬细胞增生、浆液渗出而显著增厚,肺内小血管增生、扩张。淋巴结、脾脏结构破坏,淋巴滤泡消失,脾小体萎缩,淋巴细胞明显减少,结缔组织增生。肝细胞脂肪变性,并见有多个淋巴细胞浸润灶。ISH结果显示,在肺、小肠、大脑中检测到SARS-CoV基因,其它器官中未检到,与SARS患者的检测结果基本相符。结论果子狸实验性感染SARS-CoV可导致与人类相似的病理学变化和病原分布,表明果子狸可以作为评价SARS-CoV疫苗及治疗药物的动物模型。
Objective To clarify the pathological changes of various organs of civet cats with experimental infection with SARS-CoV, the relationship between SARS-CoV and civets was further confirmed and its feasibility as an animal model of SARS was evaluated. METHODS: Human civet cats were infected experimentally with human SARS-CoV isolates BJ01 (with a 29 nucleotide deletion sequence) and GD01 (without a 29 nucleotide deletion sequence) The lung, spleen, lymph nodes, liver, small intestine, kidney, trachea, brain, pancreas, gonad, stomach and heart tissues were observed for histopathology. Meanwhile, the in situ hybridization (ISH) Distribution for testing. Results Pathological changes of lung, spleen, lymph nodes, liver, small intestine, kidney and brain were observed at different stages after challenge. The main pathological changes were lungs with acute interstitial pneumonitis, pneumoendocrinosis, alveolar serous effusion and alveolar wall Congestive, hemorrhage and lymphocytes, macrophages proliferation, serous effusion and significant thickening of small pulmonary vascular proliferation, expansion. Lymph nodes, the destruction of the spleen structure, the disappearance of lymphoid follicles, spleen body atrophy, significantly reduced lymphocytes, connective tissue hyperplasia. Hepatic steatosis, and see there are multiple lymphocyte infiltration stove. The results of ISH showed that the SARS-CoV gene was detected in the lung, small intestine and brain and not detected in other organs, which was basically consistent with the results of SARS patients. Conclusions The experimental infection of civet cats with SARS-CoV can cause similar human pathological changes and pathogenic distribution, indicating that civets can be used as animal models to evaluate SARS-CoV vaccines and therapeutic drugs.