SARS-CoV动物模型研究之中国现状

目的综合对比SARS-CoV感染的恒河猴、布氏田鼠及Lewis大鼠的病理学、免疫学以及病毒的复制与外排情况的变化,来探讨此三种动物在建立SARS模型上的特点。方法SARS病毒感染8只恒河猴、9只Lewis大鼠和20只布氏田鼠,在感染后不同时间安乐死动物,应用光镜对动物的各脏器进行病理观察研究;用病毒分离和RT-PCR方法检测病毒外排与复制的情况;用ELISA法检测动物产生特异性抗体情况。结果在SARS-CoV感染恒河猴、Lewis大鼠和布氏田鼠后,肺组织均出现一定的与人类SARS疾病相似的病理改变,在动物体内均可检测到活病毒或病毒核酸,并可检测到特异性IgG抗体的存在。在病死率上布氏田鼠最高;在病毒的复制与外排方面恒河猴的检出率最高,持续时间最长;在抗体产生情况上恒河猴与Lewis大鼠基本相似;在病理变化上恒河猴病变最重且最为复杂,与人类SARS疾病的病理变化最为接近。结论布氏田鼠,Lewis大鼠,特别是恒河猴动物模型可以用于SARS发病机制、疫苗和药物的研发,恒河猴动物模型是目前研究SARS疾病最理想的动物模型。

The Research on Animal Models for SARS in China

The SARS is a emerging infectious disease which was conformed in china firstly and spread over 37 countries and regions. Three SARS CoV animal models with Rhesus macaque, Lewis rat and Microtus brandtii were established in Institute of Laboratory Animal Science, CAMS and PUMC , China. In current paper, those SARS-CoV animal models were compared on pathological changes, immuno- response and the replication of SARS- CoV in vivo. 8 Rhesus macaques, 20 Microtus brandtii and 9 Lewis rats were infected with SARS-CoV through the nasal cavity, and sacrificed for collecting pathologic tissues on different day after inoculation. Similar pathological changes were observed in SARS CoV infected Rhesus macaques, Lewis rats and Microtus brandtii and the pathological changes was similar with SARS case of human. The SARS-CoV was carried and replicated in Rhesus macaques and last longer than Lewis rats. The infected Microtus brandtii carried SARS-CoV, but the replication of the virus was not detected by isolation and culture of the virus on Vero-E6 cell. The SARS-CoV specific IgG was detected in both of rhesus macaques and Lewis rats( The detective agents was not available for IgG of Microtus brandtii). It is interesting that SARS-CoV caused Microtus brandtii death at a rate of 10%, which is similar to the mortality of SARS on human. ON summary, the Rhesus macaques model is one of the ideal animal model to study SARS-CoV replication and vaccine and the Microtus brandtii can be used to study the lethality of SARS-CoV.