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研究生:詹錦豐
研究生(外文):Chan, Chin-Feng
論文名稱:自由基對神經細胞之致毒作用及其訊息傳遞之研究
論文名稱(外文):Studies on free radical-induced signal transduction and cytotoxicity on neuronal cells
指導教授:蕭水銀蕭水銀引用關係
指導教授(外文):Shoei-Yn Lin-Shiau, Ph.D.
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
論文頁數:192
中文關鍵詞:cerebellar granule cellsSuraminDequaliniumSodium nitroprussideThapsigarginFree radicals
相關次數:
  • 被引用被引用:0
  • 點閱點閱:199
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  • 收藏至我的研究室書目清單書目收藏:1
近年來的研究報告指出自由基(free radicals)與我們日常生活息息相關,舉凡神經退化細胞凋亡甚至於一些抗癌藥物的作用,都與其有密不可分的關係。細胞內鈣離子之調控對細胞之生長、分化及生理作用及細胞凋亡(apoptosis)等均有舉足輕重之地位,而且也是細胞內自由基產生的主要原因之一。一氧化氮(nitric oxide,NO)除了使血管放鬆的功能外亦具有使細胞凋亡和抗凋亡之雙重角色,我們日常生活經常面臨到的疼痛也受到一氧化氮的調控。我們的研究乃藉由投予dequalinium(會引發自由基產生且具很強之神經細胞毒性) 、sodium nitroprusside(一種一氧化氮提供者,NO donor) 、complete Freund Adjuvant(引發痛覺過敏,hyperalgesia)來探求一氧化氮及其他自由基致毒之機轉,並其能找到有效之拮抗劑來減低我們日常生活所面臨到之疾病。
There are more evidences indicated that free radicals play a vital role in neurodegeneration, apoptosis even in the design of cancer drugs. Regulation of intracellular calcium is crucial for cell proliferation and differentiation. It is also recognized as one of major stimuli, which can trigger free radical generation. The role of nitric oxide (NO) is not only serve as vasodilator but have duel roles on apoptosis and antiapoptosis. Furthermore, it is convinced that pain sensation is mediated by NO generation. Our results demonstrated that dequalinium (DQ) is a potent neurotoxicant accompanied by generation of free radicals. Although free radicals are so important to our life, the mechanism of its toxic effect is still not clear. In order to understand these signaling pathway, we dedicate our efforts on studying the DQ, sodium nitroprusside (SNP), and complete Freund Adjuvant (CFA, induced hyperalgesia) and try to search for the effective antagonist for medication.
封面
目錄
謝誌
目錄
圖目錄
表目錄
縮寫表
第一章 緒論
第二章 文獻回顧
第一節 類固醇與醫藥工業
第二節 類固醇化合物之微生物生物轉換
第三節 男性荷爾蒙睪固酮之生產
第四節 分枝桿菌(Mycobacteria)
第五節 醱酵生產程序之電腦應用
第三章 17β-羥基類固醇去氫之純化及性質
前言
材料與方法
一、菌種
二、培養基
三、酵素純化程序
四、蛋白質之定量
五、酵素活性之測定
六、蛋白質電泳分析
七、金屬離子及化學物質對17β-羥基類固醇去氫活性之影響測定
八、藥品
結果
一、17β-hydroxysteroid dehydrogenase之存在位置
二、17β-hydroxysteroid dehydrogenase之酵素純化
三、17β-hydroxysteroid dehydrogenase之活性染色
四、17β-hydroxysteroid dehydrogenase之酵素性質
討論
第四章 休止細胞對雄烯酮化合物之生物轉換
前言
材料與方法
一、菌種
二、培養基
三、休止細胞之製備
四、休止細胞之反應
五、類固醇之定量
六、菌體量之估算
結果
一、反應基質對生長之抑制作用
二、未添加時,不同來源休止細胞之生物轉換
三、添加時,不同來源休止細胞之生物轉換
討論
第五章 雄烯酮生產菌株Mycobacterium sp. NRRL B-3805之菌種改良
前言
材料與方法
一、菌種
二、培養基
三、菌種改良方法
四、雄烯酮收率之計算方法
結果
一、以族群篩選方式(population screening)篩選優良菌株
二、以致突變劑NTG對Mycobacterium sp. NRRL B-3805S進行變異操作
三、以原生質體融合法進行Mycobacterium sp. NRRL B-3805之種內融合
四、實驗菌株在小型醱酵槽中之生長情況
討論
第六章 類固醇化合物醱酵生產程序之改良
前言
材料與方法
一、菌種
二、培養基
三、種菌培養
四、Hinton氏三角瓶規模之生產條件探討
五、微電腦控制小型醱酵槽之操作
六、醱酵系統中容積氧氣質傳係數(Ka)之測定
七、植物(穀)固醇定量方法
八、葡萄糖殘量分析
九、菌體量之估算與類固醇化合物之定量分析
十、睪固酮產率之估算
結果
一、酸鹼值變化之影響
二、醱酵過程中酸鹼值變化之影響因子
三、醱酵系統容積氧氣質傳係數(Ka)之決定
四、Ka值對睪固酮醱酵生產之影響
五、菌體生長變因之影響
六、醱酵系統各變因關係模型之建立
七、線性化醱酵程序控制與醱酵程序之最佳化
討論
第七章 類固醇化合物之回收與精製
前言
材料與方法
一、醱酵產物之萃取回收
二、醱酵液物之吸附回收
三、瞬瀉層析法
四、薄層層析法
五、類固醇標準品懸浮液之製備
結果
一、雄烯酮醱酵產物之回收
二、雄烯酮之純化
討論
第八章 結論
中文摘要
英文摘要
參考文獻
作者小傳
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