Cox.A16型手足口病乳鼠动物模型的建立及免疫、病理特征  

Immunological and pathological characteristics of the Cox.A16-TS strain infected suckling mice

作　　者：任庆杰[1] 李敏[2] 杨晓岚[3] 管晨[4] 张广州[2] 王希良[3] 王玉光[4] 赵忠鹏[3] 

机构地区：[1]宁夏医科大学临床医学院,宁夏银川750004 [2]中国人民解放军军事医学科学院实验动物中心,北京100071 [3]中国人民解放军军事医学科学院微生物流行病研究所免疫学研究室病原微生物生物安全国家重点实验室,北京100071 [4]北京中医药大学第一临床学院中医内科,北京100029

出　　处：《中国兽医学报》2013年第11期1685-1690,共6页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(30901204);北京市自然科学基金资助项目(JJT-2010-18)

摘　　要：为建立Cox.A16型手足口病乳鼠动物模型并进行免疫、致病特性研究。将临床分离的Cox.A16病毒株经蚀斑纯化,乳鼠驯化,最终获得1株能致死11日龄乳鼠的Cox.A16毒株,命名为TS10/08(GenBank Accession NO.JX068829,Cox.A16-TS)。Cox.A16-TS感染11日龄C57BL/6J乳鼠后,观测临床疾病得分、体质量变化、死亡率并测定病毒载量、免疫分子、组织病理损伤等病毒、免疫、病理指标。结果表明,Cox.A16-TS毒株感染11日龄C57BL/6J乳鼠,其病毒毒力为50LD50/mL,感染后不同时期肌肉病毒载量均高于其他组织中,至4d达到高峰,后不断下降。至感染后6d发病达高峰时做病理检测,相对于脑组织,肌肉中有更严重的淋巴细胞浸润,引起更严重的炎性分子升高。血清中MCP-1,MIP-1alpha,MIP-1beta和CSF3动态变化,并在不同时间形成峰值。本试验初步建立了Cox.A16型手足口病乳鼠动物模型,为药物筛选、疫苗研发和免疫机理研究奠定了基础。Coxsackievirus A16 （Cox. A16） is another causative agent of epidemics of hand, foot and mouth disease other than enterovirus 71 （EV71） associated with severe complications. The patho- genesis of Cox. A16 remains unknown. In order to construct Cox. A16 infected suckling mouse model,the clinical isolates of Cox. A16 were purified by plaque purification,and adapted to suck- ling mice. Cox. A16-TS strain （JX068829） was finally achieved,which can make ll-day-old suck- ling mice infection and death. To study immunological and pathological characteristics of this model, l 1-day-old suckling mice were infected and observed the clinical disease scores, body weight changes and mortality. At 6 day post infection,viral loads of the different tissues,immune molecule levels and pathological damages of the brains and muscles were determined by real-time RT-PCR,cytometric bead array （CBA） and histopathology, respectively. The virulence of Cox. A16-TS for 11-day-old suckling mice was 50 LD50/mL. When 11-day-old suckling mice were infec- ted with Cox. A16-TS,the viral loads of muscles were higher,with a peak at 4 day post infection.At 6 day post infection,more severe necrotizing myositis and infiltration of lymphocytes were ob- served in the mice muscles. Concentrations of sera MCP-1 ,MIP-lalpha,MIP-lbeta and CSF3 were higher than those of normal mice. In conclusion,a Cox. A16 TS infected mouse model has been es- tablished,which will be used for medicine screening, vaccines development and immunopathology researches for Cox. A16-TS infection.

关 键 词：COX A16 乳鼠 免疫 病理 

分 类 号：R183.4[医药卫生—流行病学]