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系統識別號 U0026-0812200911174893
論文名稱(中文) 腸病毒71型在小鼠體內傳播途徑的探討
論文名稱(英文) The transmission route of enterovirus 71 in mice
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 92
學期 2
出版年 93
研究生(中文) 姚奕全
研究生(英文) Yi-Chuan Yao
電子信箱 yamazaki@ms21.url.com.tw
學號 s4691409
學位類別 碩士
語文別 英文
論文頁數 40頁
口試委員 指導教授-余俊強
口試委員-黎煥耀
口試委員-蘇益仁
口試委員-劉清泉
中文關鍵字 肌肉感染  肌肉麻痺  動物模式  傳播途徑  坐骨神經切斷  秋水仙素  腸病毒71型 
英文關鍵字 sciatic nerve transection  colchicine  fast axonal transport  paralysis  intramuscular injection  animal model  enterovirus 71  transmission route 
學科別分類
中文摘要   腸病毒71型是目前已知腸病毒中最晚被發現的一種,是由單股核糖核酸所組成的微小病毒。腸病毒71型容易導致嚴重的神經症狀如無菌性腦炎等,這樣的致病過程與其具有很強的神經趨向性有很大的相關。在本實驗室的研究中,腸病毒71型能夠在人類腹腔肌肉細胞瘤中進行大量的複製,比在人類神經纖維母細胞瘤中以及腸壁上皮細胞瘤中複製的能力還要強。利用本實驗室所發展出來的腸病毒71型動物感染模式中,以口服給予方式將病毒餵入七天大小鼠的胃腸道內,小鼠在感染之後會出現後肢麻痺等神經症狀,致死率高達80%。這些感染的老鼠體內可以測量到病毒累積在肌肉、腦以及脊髓中,而肌肉中的病毒量約是其他組織中病毒量的十倍之多。由此可推測肌肉細胞可能是腸病毒71型進行大量複製的場所之一。
  在肌肉注射感染七天大的小鼠實驗中,腸病毒71型可以藉著肌肉組織中的周邊神經散佈到中樞神經系統,入侵到腦和脊髓的神經細胞中,我們也發現感染的現象隨著時間經過延脊髓向上散佈至腦幹。若在感染前一天先利用快速軸突神經傳導抑制劑秋水仙素作肌肉注射,可以有效地降低從肌肉神經散佈到中樞神經的病毒量,但是這樣的效果卻沒有辦法以坐骨神經切斷術來達到。另外,在腦內注射腸病毒71型感染七天大的小鼠體內,我們也發現嚴重的神經細胞損害以及肌肉細胞壞死,這兩種組織中也都含有高量的病毒力價,這也顯示不僅只有從肌肉感染腸病毒71型會散佈到中樞神經,而從腦內直接感染的方式也會導致病毒散佈到肌肉當中。由以上實驗結果,我們證實腸病毒71型不僅具有神經趨向性,更具有強烈的肌肉趨向性;透過肌肉組織中的周邊神經,腸病毒71型能利用快速軸突神經傳導的方式散佈到中樞神經系統中,引發嚴重的神經症狀。這也讓我們更了解腸病毒71型的致病過程與機制。
英文摘要   Enterovirus 71 (EV71) is a single positive-stranded RNA virus with strong neurotropism, which is probably attributed to its pathogenesis. Our studies showed that EV71 propagated more effectively in the human rhabdomyosarcoma cells (RD) than in the neuroblastoma cells (SK-N-SH) and colorectal adenocarcinoma cells (Caco-2). After oral inoculation of a mouse-adapted EV71 strain, seven-day-old ICR mice developed neurological diseases with a mortality rate of 50~80%. A large amount of viruses accumulated in the muscle, brain and spinal cord, indicating muscle was a major replication site for EV71.
  Neuroinvasion was observed in intramuscularly infected mice, indicating EV71 might spread to the central nervous system (CNS) from peripheral nerves in muscle. After intramuscular infection, viral titer in spinal cord was reduced in colchicine-treated mice but not in sciatic-nerve-transected mice. With intracranial infection of EV71, mice developed severe neuronal damage and muscle necrosis. Both tissues contained high viral titer. These results indicate that EV71 possesses strong myotropism and fast axonal transport might represent a major route for spreading of EV71 to the CNS.
論文目次 Contents 1
Figure list 2
Introduction 3
Experimental design 8
Materials and methods 11
Results 20
Discussion 25
References 27
Appendix 1. 39
Appendix 2. 40
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