羊瘙痒因子263K经灌胃感染仓鼠动物模型的建立  

Scrapie strain 263K can induce spongiform encephalopathy in golden hamster by intragastrical injection

作　　者：张瑾[1] 陈岚[2] 肖新莉[1] 张宝云[3] 韩俊[3] 高建梅[3] 姜慧英[3] 刘勇[1] 董小平[3] 

机构地区：[1]西安交通大学医学院,陕西西安710061 [2]中国医学科学院基础医学研究所,中国协和医科大学基础医学院,医学分子生物学国家重点实验室,北京100005 [3]中国疾病预防控制中心病毒病预防控制所,北京100052

出　　处：《西安交通大学学报（医学版）》2005年第2期119-123,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金委重点项目(No.30130070);国家863计划项目(No.2001AA215391);欧盟项目(QLRT 2000 01441);国家科技攻关计划项目(No.2003BA712A04-02).

摘　　要：目的　胃肠感染是大多数动物类传染性海绵状脑病(TSE)传播的最主要途径。建立羊瘙痒因子263K灌胃感染仓鼠动物模型,并研究其发病特征。方法　Scrapie 263K毒株低剂量和高剂量经灌胃途径接种金黄仓鼠,在终末期取脑组织,用HE染色观察病理变化,免疫组化法检测PrPSc 的组织沉积特点, Western blot 检测PrPSc 分子特征。结果　低剂量灌胃组仅一只动物发病,高剂量组所有接种动物均发病,潜伏期较颅内注射组明显延长。在脑组织中观察到典型的病理改变;PrPSc免疫组化检测显示弥漫性沉积于脑组织,主要累及脑干、大脑皮层深层、小脑,基本与病理学改变累及的区域一致;Western Blot检测发现感染动物脑提取物出现可抵抗蛋白酶消化的PrPSc条带,与颅内注射组脑组织提取物中PrPSc电泳性状完全一致。结论　羊瘙痒因子263K灌胃可成功引起动物发病,与颅内注射比较,潜伏期、神经病理变化和PrPsc沉积均有不同,可能受到感染途径的影响。Objective Ingestion of the infectious agent is a major way of the spreading of transmissible spongiform encephalopathy (TSE) among animals. In this study, the infectious characteristics of the hamster-adapted scrapie strain 263K infecting hamsters by intragastrical injection (i.g.) were identified. Methods Golden hamsters were challenged through intragastrical injection with low and high dosage scrapie 263K. At the terminal stage of clinical course, all animals were sacrificed and the brain were dissected. The pathological changes, PrP Sc deposits and patterns of PK-resistant PrP were analyzed by HE staining, immunohistochemistry (IHC) assay and Western blot. Results One out of eight animals showed clinical signs at the incubation of 185 days with low dosage. All animals showed clinical signs at the average incubation of 105 days with high dosage. The typical pathological changes were found in brain tissues. PrP Sc specific immunohistochemistry assay revealed a large amount of PrP Sc deposits scattering in brain. The most remarkable spongiform degeneration and PrP Sc deposits were found in brain stem, cerebrum and cerebellum. Protease resistant PrP Sc was detected in brain with Western blot, showing the same electrophoresis patterns as that of brain tissues from animals with intracerebral inoculation. Conclusion These data imply that typical TSE could be induced in hamsters by inoculating strain 263K in intragastrical injection. The incubation periods and characteristics of neuropathological changes and PrP Sc deposits depend on the infective pathway.

关 键 词：羊瘙痒病 263K 灌胃 PrP^Sc 

分 类 号：R373[医药卫生—病原生物学]