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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林靖愉 | |
dc.contributor.author | Meng-Hsuan Chung | en |
dc.contributor.author | 鍾孟軒 | zh_TW |
dc.date.accessioned | 2021-06-16T17:22:17Z | - |
dc.date.available | 2016-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-17 | |
dc.identifier.citation | Barabasi A.L., Oltvai Z., et al. (2004). Network biology: understanding the cell's functional organization nature reviews. Genetics, 5: 101-113.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63895 | - |
dc.description.abstract | 萘是常見的多環芳香烴,萘廣泛的運用在生活製品中且因為它的易揮發性,使人類於日常生活中容易不經意地暴露過量的萘,然而萘的毒性作用機制目前仍不完全清楚。代謝體學透過完整地分析內生性代謝物的變化,可以了解外來物在生物體內的生物效應,藉由核磁共振光譜儀的代謝體學方法能全面的研究萘對小鼠各組織代謝的影響並探討萘的毒性機制。
本研究利用腹腔注射ICR品種的小鼠進行劑量反應實驗,共三組:對照組(橄欖油)、100 mg/kg及200 mg/kg的萘劑量,接著利用核磁共振光譜儀分析、主成分分析(PCA)及正交偏最小二乘判别分析(OPLS-DA)來研究肺、肝及腎組織的代謝體變化。從研究結果發現,三種組織經由實驗處裡的代謝反應皆可由主成分分析加以區分,並經傳統統計檢驗發現許多重要代謝物呈現顯著變化;萘對肺組織的影響可能包括細胞膜結構的損害及粒線體能量代謝的干擾,分別反映在Glycerophosphocholine量的下降及Succinate的上升,而萘對肝及腎組織的影響與抗嗜電子性化合物(electrophiles) 反應機制有很高的相關,肝組織中Glutamine和UDP-glucose隨萘暴露劑量提高呈現顯著上升,腎組織中Glutathione的量也隨萘暴露劑量增加呈顯著上升,這可能表示萘暴露啟動了肝及腎組織的解毒機制。 我們的研究結果顯示萘對小鼠的毒性作用不只會影響主要標的器官肺,對於肝及腎組織的代謝體同樣會造成影響,透過代謝物的影響可以部分解釋萘對小鼠的病理結果,本研究也證明了核磁共振儀的代謝體學研究方法對於了解毒性作用機制是相當有力的工具。 | zh_TW |
dc.description.abstract | Naphthalene, a primary polycyclic aromatic hydrocarbon (PAH), widely spread in the environment was hypothesized to relate with adverse health effects. In order to clarify the underlying mechanisms of naphthalene-induce toxicity, extensive studies are required. Therefore, this study intended to investigate the mechanisms of naphthalene-induce toxicity in various tissues of mice. We used high through-put 1H NMR-based metabolomics to study effects of naphthalene on mouse tissues. Dose-response experiments (0, 100 and 200 mg/kg naphthalene, ip) were carried out on male ICR mice. Both hydrophilic and hydrophobic metabolites from the lung, liver and kidney tissues were extracted and analyzed by 1H and p-J-resolved NMR followed by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA). From our results, the metabolic effects of naphthalene on lung, liver, and kidney demonstrated dose-dependent effects. Our results suggest that naphthalene-induced lung injures were associated with cellular membrane damages and turbulence of energy metabolisms, where declination of glycerophosphocholine and increase of succinate was found in the lung. In the liver, glutamine and UDP-glucose were increased in the 200 mg/kg exposure group. Besides, detoxification nucleophile glutathione, also demonstrated to be increased depending on naphthalene dose in the kidney. Through this study, not only the metabolome of target organ lung but metabolome of liver and kidney were found to respond to naphthalene intervention. The changes of these metabolites may partially explain the pathological response of naphthalene exposure. In conclusion, 1H NMR-based metabolomics is a useful tool in understanding the mechanism of xenobiotic induced toxicities. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:22:17Z (GMT). No. of bitstreams: 1 ntu-101-R99844011-1.pdf: 2321951 bytes, checksum: 1ce196810918812cc4f6d6606c11e606 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 國立台灣大學碩士學位論文口試委員會審定書……………………………….I
誌謝 ……………………………………………………………………………….II 摘要 ……………………………………………………………………………….III Abstract …………………………………………………………………………..IV 目錄 ……………………………………………………………………………….V 圖目錄 …………………………………………………………………………….VII 表目錄 …………………………………………………………………………….IX 第一章 前言………………………………………………………………….1 1.1 萘簡介………………………..…………………………………………1 1.1.1 物理化學特性及健康危害………………………………………….1 1.1.2 暴露來源………………………………………………………….....2 1.1.3 代謝排除…………………………………………………………….2 1.1.4 各物種間萘對肺及呼吸組織毒性………………………………….3 1.1.5 萘對肝及腎組織的影響…………………………………………….5 1.1.6 萘對生物代謝體的影響…………………………………………….6 1.2 代謝體學研究…………………………………………………………...7 1.2.1 代謝體學簡介………………………………………………………..7 1.2.2 代謝體學研究流程…………………………………………………..8 1.2.3 代謝體學研究策略及未來展望……………………….…………….10 1.3 核磁共振光譜儀………………………………………………...11 1.3.1 核磁共振光譜儀原理………………………..………………………11 1.3.2 核磁共振光譜儀的優缺點及展望…………………………………..13 1.4 研究設計背景…………………………………………………………...14 1.5 研究目的………………………………………………………………...15 第二章 實驗材料與方法………………………………….…………………..16 2.1 實驗架構…………………………………………………………..……..16 2.2 動物實驗處理……………………………………………………..……..17 2.3 代謝體學實驗方法………………………………………………..……..18 2.3.1 樣本處裡………………………..…………………………………….18 2.3.2 核磁共振光譜儀分析方法…………………………………………...19 2.3.3 核磁共振光譜處理及資料分析……………………………………...21 第三章 結果……………..……………………………………………………..24 3.1 核磁共振光譜分析結果………………………………………………….24 3.2 各組織綜合結果………………………………………………………….24 3.3 肺臟組織………………………………………………………………….25 3.4 肝臟組織………………………………………………………………….27 3.5 腎臟組織………………………………………………………………..28 第四章 討論………………………………………………………………….30 4.1 綜合結果討論…………………………………………………………..30 4.2 萘暴露對肺臟組織代謝體之影響……………………………………..32 4.3 萘暴露對肝臟組織代謝體之影響……………………………………..35 4.4 萘暴露對腎臟組織代謝體之影響……………………….…………….37 4.5 研究限制………………………………………………….…………….38 4.6 結論……………………………………………………………………..39 參考文獻…………………………………………………………………………..40 | |
dc.language.iso | zh-TW | |
dc.title | 利用核磁共振光譜儀的代謝體學來研究萘對小鼠組織的影響 | zh_TW |
dc.title | 1H NMR-based Metabolomics to Study Effects of Naphthalene on Mouse Tissues | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳焜裕,郭錦樺,唐川禾 | |
dc.subject.keyword | 萘,小鼠,肺部疾病,肝,腎,核磁共振光譜儀,代謝體學, | zh_TW |
dc.subject.keyword | naphthalene,mouse,lung toxicity,liver,kidney,NMR,metabolomics, | en |
dc.relation.page | 97 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-17 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 環境衛生研究所 | zh_TW |
顯示於系所單位: | 環境衛生研究所 |
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