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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 | Feng-Peng Huang | en |
dc.contributor.author | 黃豐斌 | zh_TW |
dc.date.accessioned | 2021-06-16T10:56:20Z | - |
dc.date.available | 2018-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-08 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61256 | - |
dc.description.abstract | 萘是環境中常見的多環芳香烴,許多研究指出當小鼠暴露在萘後會造成呼吸道非纖毛細胞(Clara細胞)的嚴重傷害;然而當小鼠重複暴露於萘卻能使Clara 細胞對萘的傷害產生抵抗。為了釐清萘的單一劑量暴露與重複暴露所引發的毒理及解毒機制,藉由核磁共振光譜儀為基礎的代謝體學能了解小鼠各組織在不同萘暴露方式之下內生性代謝物的變化,並探討萘毒性耐受性小鼠在萘暴露下可能的毒理及解毒機制。
本研究利用腹腔注射ICR品種的雄性小鼠進行動物實驗,對照組連續八天注射橄欖油;單一劑量暴露組連續七天注射橄欖油,再於第八天注射300 mg/kg萘;重複劑量暴露組則連續七天注射200 mg/kg萘,再於第八天注射300 mg/kg萘。24小時後犧牲採集肺、肝、腎臟組織及支氣管肺泡沖洗液,接著利用核磁共振光譜儀分析及主成分分析來研究各組織的代謝體變化。從研究結果發現,各組織在單一萘劑量暴露與重複萘暴露後的代謝反應皆可由主成分分析加以區分,經傳統統計檢定後發現許多重要代謝物有顯著變化。呼吸系統在單一劑量暴露組及重複暴露組出現的代謝物變化和能量代謝干擾及細胞膜結構損害有關,此外重複暴露還會誘發Glutathione 所主導的抗氧化機制並對萘的傷害產生耐受性,但重複暴露之下也有引發肺腫瘤細胞的疑慮,分別反應在Glucose量的下降及Glutamine量的上升。我們的結果也指出不只在呼吸系統這個主要的標的會受到萘重複暴露的影響,肝臟及腎臟組織也都會有能量擾動的情形。 透過代謝體的分析可以部分解釋不同萘暴露方式對小鼠的毒性作用,尤其是過去較少研究的重複暴露所引發的毒性耐受性,本研究也證明了核磁共振光譜儀為基礎的代謝體學研究方法對於了解環境毒物的毒理機制是相當有力的工具。 | zh_TW |
dc.description.abstract | Naphthalene which is widely spread in the environmental is a common polycyclic aromatic hydrocarbon. Several studies indicated that single dose exposure of naphthalene cause acute injury on mouse Clara cell, a bronchiolar epithelial cell type. However, when mice are administered repeated doses of naphthalene, the susceptible Clara cell become refractory to injury. In this study, we intended to investigate the mechanisms of naphthalene toxicity in various mouse tissues among injured, tolerant, and the control mice using 1H NMR-based metabolomics. Male ICR mice were administered seven repeated injections (ip) of NA (0, 200 mg/kg/day; single and repeated naphthalene exposure, respectively) in olive oil and gave a challenge dose (300 mg/kg/day) at eighth day. Bronchoalveolar lavage fluid and both hydrophilic and hydrophobic extracts from the lung, liver and kidney were analysed by 1H NMR followed by principal component analysis. Our results showed that, the metabolites effect of single naphthalene which cause cell injury on respiratory system are associated with cellular membrane damages and energy metabolism disturbance. However, the repeated exposure may induce the antioxidation mechanism associated with glutathione;
Therefore mice become tolerant to naphthalene. In addition, we also suspected that repeated exposed to naphthalene would cause lung tumor development, since declination of glucose and increase of glutamine was found in the lung of repeated exposure group. In the liver, the upregulation of glutathione in repeated exposure mice may play an important role in leading to naphthalene toxicity tolerance, too. The metabolome disturbance of single exposure in the liver and kidney are associated with energy metabolism. In this study, we have partially explained the mechanisms of naphthalene toxicity and detoxification within single dose and repeated exposure. In conclusion, 1H NMR-based metabolomics is useful in understanding the toxicity and detoxifying mechanisms due to xenobiotic interventions. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T10:56:20Z (GMT). No. of bitstreams: 1 ntu-102-R00844009-1.pdf: 16740601 bytes, checksum: 3fbfea4d0b285a410902e120f00c9019 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 目錄
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 v 目錄 vii 圖目錄 x 表目錄 xiii 第一章 前言 1 1.1研究緣起 1 1.2研究目的 2 第二章 文獻探討 3 2.1萘的簡介 3 2.1.1萘的特性 3 2.1.2萘的吸收、分佈、代謝及排除 (ADME) 4 2.1.3 萘的急性及慢性毒性 5 2.1.4 萘在單一劑量暴露下的肺部毒性 6 2.1.5 萘在重複暴露下的毒性耐受性 7 2.2代謝體學研究 9 2.2.1體學發展 9 2.2.2 代謝體學介紹 10 2.2.3 代謝體學研究流程 10 2.3核磁共振光譜儀 13 2.3.1 核磁共振光譜儀原理 13 2.3.2 核磁共振光譜儀圖譜資訊 14 第三章 實驗材料與方法 16 3.1 病理組織切片(Histopathology)實驗架構 16 3.2病理組織切片動物實驗處理 17 3.3 病理組織切片製作 17 3.4 代謝體學實驗架構 18 3.5 代謝體學動物實驗處理 19 3.6 代謝體學實驗方法 20 3.6.1 支氣管肺泡沖洗液採集及處理 20 3.6.2 組織樣本處理 20 3.6.3 核磁共振光譜儀分析方法 21 3.6.4 核磁共振圖譜處理及分析 24 第四章 結果 26 4.1 肺臟組織病理學切片結果 26 4.2 核磁共振光譜儀分析結果 26 4.3 萘單一劑量或重複暴露對肺臟代謝體的影響 26 4.4萘單一劑量或重複暴露對支氣管肺泡沖洗液代謝體的影響 28 4.5萘單一劑量或重複暴露對肝臟代謝體的影響 29 4.6萘單一劑量或重複暴露對腎臟代謝體的影響 31 第五章 討論 33 5.1 萘單一劑量或重複暴露對呼吸系統代謝物之影響 34 5.2萘單一劑量或重複暴露對肝臟組織代謝物之影響 38 5.3萘單一劑量或重複暴露對腎臟組織代謝物之影響 39 5.4 研究限制 40 5.5 結論 41 參考文獻 42 | |
dc.language.iso | zh-TW | |
dc.title | 利用核磁共振光譜儀為基礎的代謝體學探討萘毒性耐受性小鼠在萘暴露下的毒理機制 | zh_TW |
dc.title | 1H NMR-based Metabolomics to Study Naphthalene Toxicity in A Tolerant Mouse Model | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳焜裕,郭錦樺,唐川禾 | |
dc.subject.keyword | 萘,毒性,耐受性,肺,支氣管肺泡沖洗液,glutathione,代謝體學,核磁共振光譜儀, | zh_TW |
dc.subject.keyword | naphthalene,toxicity,tolerant,lung,BALF,glutathione,metabolomics,nuclear magnetic resonance (NMR), | en |
dc.relation.page | 101 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-09 | |
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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