The 53rd annual meeting of the Japanese Association for Laboratory Animal Science

[目的]探讨乙型肝炎病毒(HBV)转基因小鼠模型筛选抗HBV药物的可行性。[方法]用公认抗HBV复制药物拉米夫定对我们建立高复制HBV转基因鼠进行实验,选我们建立的1.3copy高复制HBV转基因小鼠20只,随机分成两组,每组10只。采用灌胃针灌胃法给药。对照组灌喂生理盐水,实验组灌喂拉米夫定,剂量为100mg/kg,每天2次,连续灌21d,每7d采血1次。荧光定量PCR检测血清中HBVDNA。[结果]实验组用拉米夫定前小鼠血清HBVDNA5.50±0.42(拷贝数log10数值),3周后HBVDNA已显著降低(4.63±0.57),4周后,小鼠血清HBVNDA为4.08±0.51,停药1周后,再次检测血清HBVDNA,小鼠血清HBVDNA又恢复正常水平(5.70±0.39)。[结论]我们建立的高复制HBV转基因小鼠模型验证了拉米夫定对HBV复制的抑制程度和持续时间,表明该模型可应用于抗HBV药物的筛选、评价研究。

Usage of HBV Transgenic Mice in Evaluation of Antiviral Drug Lamivudine

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.