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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 魏嘉徵(Chia-Cheng Wei) | |
| dc.contributor.author | Nien-Chieh Yang | en |
| dc.contributor.author | 楊念潔 | zh_TW |
| dc.date.accessioned | 2022-11-25T07:45:43Z | - |
| dc.date.available | 2023-09-03 | |
| dc.date.copyright | 2021-09-29 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-09-06 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82492 | - |
| dc.description.abstract | "玉米赤黴烯酮 (zearalenone) 為一種由鐮刀菌屬所產生的黴菌毒素，常見於燕麥、小麥、大麥與玉米中，因其結構與雌二醇相似，故過去研究多探討其生殖毒性；然而，對於其與神經退化性疾病的關聯與機制探討等相關研究則較缺乏。且臺灣在2018年由食品藥物管理署公布之《食品中污染物質及毒素衛生標準》中，亦新增zearalenone在食品裡的限量濃度，可見為亟需關注的食品安全議題之一。因此本研究以模式生物秀麗隱桿線蟲 (Caenorhabditis elegans, C. elegans)，探討暴露不同濃度zearalenone是否會造成生物體產生神經退化性疾病相關的病徵與其背後調控的機制為何。研究結果顯示，暴露1.25、10及50 μM zearalenone，會誘發C. elegans產生帕金森氏症相關的兩大病徵，一為顯著提高C. elegans體內α-突觸核蛋白 (α-synuclein) 的累積量，二為顯著增加C. elegans多巴胺神經元之退化情形；進一步觀察C. elegans與多巴胺神經元相關之食物敏感行為與游泳誘導麻痺等運動行為發現，在暴露1.25、10及50 μM zearalenone的條件下，會影響食物敏感行為；在10及50 μM zearalenone暴露下會提升游泳誘導麻痺的比例，證明zearalenone的暴露會產生與多巴胺神經元相關之神經毒性。本研究進一步分析細胞凋亡和細胞自噬途徑相關基因之表達量，顯示50 μM zearalenone的暴露下會活化細胞凋亡並抑制細胞自噬機制，同時亦觀察到zearalenone會造成C. elegans體內粒線體含量的累積與粒線體分裂比例提高。推測為細胞凋亡機制中的drp-1活化導致粒線體斷裂並加速細胞凋亡的發生，因此更進一步使用drp-1突變種C. elegans 進行探討，發現50 μM zearalenone暴露並不會對drp-1突變種造成食物敏感行為的改變；此外，應用drp-1 RNAi技術於轉基因C. elegans亦發現50 μM zearalenone暴露不會加重多巴胺神經元的損傷，顯示drp-1與zearalenone造成之神經毒性有直接關係。綜合本研究之結果，zearalenone的暴露會對C. elegans造成神經毒性，且會影響細胞自噬與細胞凋亡途徑基因的表達，並透過drp-1加速多巴胺神經元損傷的神經毒性效應。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T07:45:43Z (GMT). No. of bitstreams: 1 U0001-3108202110120800.pdf: 2081620 bytes, checksum: 8a246754e9f7ce8ce371d009178ce4db (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定書 i 誌謝 ii 摘要 iii Abstract iv Graphic Abstract vi Highlights vii 目錄 viii 圖次 x 表次 xi 1. 研究動機與研究問題 1 2. 文獻回顧與研究目的 3 2.1 玉米赤黴烯酮 (Zearalenone) 3 2.2 Zearalenone汙染狀況 3 2.3 Zearalenone相關規範 4 2.4 Zearalenone生物毒理性質 7 2.4.1 吸收、分佈、代謝與排除 7 2.4.2 生殖毒性 8 2.4.3 免疫毒性 8 2.4.4 肝毒性 9 2.4.5 致癌毒性 10 2.4.6 基因毒性 10 2.5 以秀麗隱桿線蟲 (Caenorhabditis elegans) 探討zearalenone之毒性 12 2.5.1 C. elegans 12 2.5.2 利用C. elegans探討神經退化性疾病帕金森氏症 12 2.6 研究目的 14 3. 研究材料與方法 15 3.1 實驗架構流程圖 15 3.2 實驗藥品 16 3.3 C. elegans 培養 16 3.4 C. elegans體內α-synuclein蛋白累積之試驗 16 3.5 C. elegans多巴胺神經元觀察之試驗 17 3.6 C. elegans食物敏感行為 (Basal Slowing) 之試驗 18 3.7 C. elegans游泳誘導麻痺 (Swimming-induced Paralysis) 之試驗 18 3.8 C. elegans體內粒線體含量之試驗 19 3.9 C. elegans體內粒線體型態觀察之試驗 19 3.10 即時定量聚合酶連鎖反應 (qRT-PCR) 20 3.11 核糖核酸干擾之試驗 (RNA Interference, RNAi) 20 3.12 統計分析 21 4. 研究結果與討論 22 4.1 Zearalenone對C. elegans體內α-synuclein蛋白累積量之影響 22 4.2 Zearalenone對C. elegans多巴胺神經元之影響 24 4.3 Zearalenone對C. elegans多巴胺神經元相關行為之影響 28 4.4 Zearalenone對C. elegans細胞中粒線體之影響 33 4.5 Zearalenone對C. elegans細胞凋亡相關基因之影響 38 4.6 Zearalenone對C. elegans細胞自噬相關基因之影響 41 4.7 drp-1對zearalenone 暴露所誘導C. elegans相關損傷之調控 44 5. 結論 48 6. 建議 49 7. 參考文獻 50 8. 附錄 67 " | |
| dc.language.iso | zh-TW | |
| dc.subject | 帕金森氏症 | zh_TW |
| dc.subject | 粒線體功能障礙 | zh_TW |
| dc.subject | 玉米赤黴烯酮 | zh_TW |
| dc.subject | 神經退化性疾病 | zh_TW |
| dc.subject | 秀麗隱桿線蟲 | zh_TW |
| dc.subject | neurodegeneration diseases | en |
| dc.subject | mitochondrial dysfunction | en |
| dc.subject | Parkinson’s disease | en |
| dc.subject | zearalenone | en |
| dc.subject | C. elegans | en |
| dc.title | 玉米赤黴烯酮對秀麗隱桿線蟲誘導帕金森氏症毒性及相關機制之探討 | zh_TW |
| dc.title | Evaluation of Zearalenone Toxicity on Parkinson’s Disease and the Underlying Mechanisms in Caenorhabditis elegans | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 何元順(Hsin-Tsai Liu),潘敏雄(Chih-Yang Tseng),洪偉倫 | |
| dc.subject.keyword | 秀麗隱桿線蟲,玉米赤黴烯酮,神經退化性疾病,帕金森氏症,粒線體功能障礙, | zh_TW |
| dc.subject.keyword | C. elegans,zearalenone,neurodegeneration diseases,Parkinson’s disease,mitochondrial dysfunction, | en |
| dc.relation.page | 69 | |
| dc.identifier.doi | 10.6342/NTU202102904 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-09-07 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 食品安全與健康研究所 | zh_TW |
| dc.date.embargo-lift | 2023-09-03 | - |
| 顯示於系所單位： | 食品安全與健康研究所 | |
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