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研究生: 李奕均
Li, Yi-Jiuen
論文名稱: 利用細胞色素氧化酵素活性的形態學研究探討 Wernicke encephalopathy 症狀的成因
The morphological study about cytochrome oxidase activity in Wernicke encephalopathy
指導教授: 簡基憲
Chien, Chi-Hsien
學位類別: 碩士
Master
系所名稱: 醫學院 - 細胞生物與解剖學研究所
Institute of Cell Biology and Anatomy
論文出版年: 2007
畢業學年度: 95
語文別: 中文
論文頁數: 73
中文關鍵詞: 硫胺素缺乏細胞色素氧化酵素
外文關鍵詞: cytochrome oxidase, thiamine deficiency
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  • Wernicke encephalopathy常發生在酗酒者身上,正常人營養失調也會導致此病(Andersen 2004)。Wernicke encephalopathy引發身體功能失調的症狀包含眼球運動障礙、運動失調以及心智混亂。目前已知此症狀是因硫胺素缺乏所致,但缺乏硫胺素導致Wernicke encephalopathy症狀的原因並不清楚,臨床治療經靜脈注射硫胺素後症狀便能改善。硫胺素是粒腺體中pyruvate dehydrogenase complex與α-ketoglutarate dehydrogenase complex的輔酶,硫胺素缺乏造成能量代謝障礙,最後影響電子傳遞鏈的進行。電子傳遞鏈中最後催化酵素是細胞色素氧化酵素,所以神經細胞能量代謝的高低可藉由觀察細胞色素氧化酵素活性的高低作為指標。本論文將著重於觀察硫胺素缺乏對腦幹中動眼、小腦以及其它神經核群所造成的影響,並且以滾輪試驗與足跡試驗觀察運動協調性。結果顯示硫胺素缺乏造成動眼、小腦和聽覺神經核群的細胞色素氧化酵素活性下降,且伴隨體重減輕與眼球運動障礙。小腦協調性的試驗中,在滾輪上運動的時間明顯下降且足跡測試中亦出現不正常步態。因Wernicke encephalopathy的症狀可補充硫胺素改善,回復組中動眼、小腦和聽覺神經核群細胞色素氧化酵素活性明顯回升且症狀改善,說明了倉鼠產生的症狀類似Wernicke encephalopathy。本研究結果證實硫胺素缺乏造成眼球控制與協調運動神經核群的能量代謝明顯下降,進而出現類似Wernicke encephalopathy的症狀。本實驗的結果對Wernicke encephalopathy症狀提供一個型態學的證據與可能的解釋。

    Wernicke encephalopathy was found in alcoholics most frequently, but it was also found in disorders associated with malnutrition. The symptoms are including ophthalmoparesis, ataxia, and acute mental confusion. Wernicke encephalopathy is a serious of disorder caused by thiamine deficiency (TD), although the mechanism is still not clear. It was demonstrated that the intravenous injection with thiamine results in quickly recovery of Wernicke encephalopathy symptoms. Thiamine is an important factor in TCA cycle to ensure mitochondrial metabolism successfully. Thiamine deficiency induces metabolic disorders of downstream reactions including electron transport chain. In the other hand, cytochrome oxidase (COX) is the terminal enzyme in the electron transport chain and is a marker of neuronal activity to examine metabolic changes. In this study, we focused on the influence of thiamine deficiency on Wernicke encephalopathy by performing histochemical methods to elucidate the distribution pattern of cytochrome oxidase in brainstem among ocular motor system、cerebellar system and other system. In the experimental group, we performed the foot printing test and the rotarod test to investigate the changes in motor coordination and balance in thiamine deficiency animal. In addition, we have also observed the eye movements and weight variations to confirm our previous result. The results showed a significant decrease in the cytochrome oxidase activity among ocular motor nuclei, cerebellar nuclei and even auditory nuclei in light microscopic study. In addition, the results also showed that not only significant dropped weights but also bumpy movements were observed in thiamine deficiency animals compared with the normal animals. Furthermore, the animals were significantly improved in motor coordination and the cytochrome oxidase activities were increased immediately in recovery group. Those findings provide possible pathological explanation for the thiamine deficiency induce Wernick encephalopathy.

    中文摘要…………………………………………………………I 英文摘要…………………………………………………………III 誌謝………………………………………………………………V 目錄………………………………………………………………VI 緒論………………………………………………………………1 材料與方法………………………………………………………8 結果………………………………………………………………15 討論………………………………………………………………20 結論………………………………………………………………29 圖表說明…………………………………………………………30 參考文獻…………………………………………………………67 自述………………………………………………………………73

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