四环素对朊病毒羊瘙痒因子263K蛋白酶抗性和感染性的影响  

Effects of tetracycline on protease-resistant activity and the infectivity of scrapie strain 263K

作　　者：郭燕军[1] 韩俊[2] 姚海兰[2] 张宝云[2] 高建梅[2] 肖新莉[2] 赵伟秦[1] 王得新[1] 董小平[2] 

机构地区：[1]首都医科大学附属北京友谊医院神经内科,北京100050 [2]中国疾病预防控制中心病毒病预防控制所

出　　处：《中华神经科杂志》2005年第5期313-316,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金委重点项目(30130070);国家“863”计划项目(2004AA215140);欧盟项目(QLRT200001441);国家科技攻关计划资助项目(2003BA712A04-02)

摘　　要：目的研究四环素对朊病毒羊瘙痒因子263K(PrPSc)体外蛋白酶抗性和实验动物感染性的影响。方法以不同浓度的四环素与PrPSc进行不同时间的作用,经蛋白酶K的处理后以Westernblot方法检测具有蛋白酶抗性的PrPSc蛋白;将经四环素处理的PrPSc样品分组颅内接种金黄地鼠,观察动物发病,以Westernblot方法检测发病动物脑组织中PrPSc的存在情况。结果四环素与PrPSc的体外作用可明显地降低或消除PrPSc对蛋白酶K消化的抵抗能力,并呈明显的剂量效应相关性。与对照组相比[平均潜伏期(53.75±0.50)d],经5mmol/L和20mmol/L四环素处理的高滴度PrPSc样品的实验动物感染潜伏期延长,潜伏期分别为(61.50±1.73)d(P<0.01)和(59.50±0.58)d(P<0.05),差异有统计学意义。结论四环素能够有效降低PrPSc的体外蛋白酶抗性,并延长PrPSc感染动物发病潜伏期。ObjectiveTo observe the possible effectiveness of tetracycline on protease-resistant activity in vitro and the infectivity in vivo of a scrapie strain 263K(PrP^(Sc)).MethodsScrapie agents were incubated with different concentrated tetracycline for various periods and the protease-resistant PrP^(Sc) signals were evaluated with proteinase K-treatment Western blots. The preparations treated with tetracycline were intracerebrally inoculated into golden hamsters and the typical transmissible spongiform encephalopathy manifestations were noted. The presences of PrP^(Sc) in brain tissues of the diseased animals were detected with PrP^(Sc) specific Western blot assays.ResultsWestern blot assays showed that the amounts of protease-resistant PrP^(Sc) were significantly reduced or removed in the preparations treated with tetracycline, revealing a remarkable dose-dependant phenomenon. Compared with the control group with the mean incubation time (53.75±0.50) days, inoculations with the preparations treated with 5 mmol/L and 20 mmol/L tetracycline could prolong the incubation time of the infected animals, whose mean incubation time was (61.50±1.73) and (59.50±0.58) days, respectively, showing a statistic difference.ConclusionTreatment of scrapie agent 263K with tetracycline might reduce or remove its protease-resistant activity in vitro and prolong the incubation time of infected hamsters.

关 键 词：四环素 蛋白酶 感染性 朊病毒 抗性 因子 瘙痒 PrP^Se Western 羊 blot 潜伏期延长 mol/L moL/L 发病潜伏期 实验动物 不同时间 不同浓度 金黄地鼠 颅内接种 存在情况 抵抗能力 体外作用 剂量效应 动物感染 感染动物 

分 类 号：R742.89[医药卫生—神经病学与精神病学]