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研究生: 陳一喆
Chen, Yi-Zhe
論文名稱: 利用SWATH-MS分析小鼠小腸中塑膠微粒毒性的差異蛋白質體學
Differential proteomics of microplastic toxicity in mouse small intestine using SWATH-MS
指導教授: 陳頌方
Chen, Sung-Fang
口試委員: 陳頌方
Chen, Sung-Fang
陳百昇
Chen, Pai-Sheng
陳怡婷
Chen, Yi-Ting
口試日期: 2024/07/22
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2024
畢業學年度: 112
語文別: 中文
論文頁數: 93
中文關鍵詞: 塑膠微粒聚苯乙烯蛋白質體學SWATH
英文關鍵詞: polystyrene, microplastic, proteomics, SWATH
DOI URL: http://doi.org/10.6345/NTNU202401493
論文種類: 學術論文
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  • 由於人類大量釋放塑膠垃圾於環境中,這些垃圾會被逐一分解成顆粒更小的塑膠微粒,並可能經由食物鏈回到人體,產生生物放大作用的影響。先前文獻指出,塑膠微粒會在哺乳動物的胃腸道、肝臟、腎臟和大腦中積累。本研究利用SWATH這項無標記定量的質譜技術,分析小鼠小腸中的聚苯乙烯微粒實驗組和控制組的差異蛋白質。先將胜肽進行第一維的鹼性逆向層析分離後,再送到後續奈米液相層析串聯質譜分析(nanoLC-MS/MS)。本研究不僅成功地鑑定到3666蛋白質及其31501的胜肽片段,同時也用SWATH方法定量出2933個蛋白質。在實驗組和控制組中有473個蛋白質表現量具有顯著差異。藉由GO和Metascape分析,可以看到這些具有差異性的蛋白質主要和細胞凋亡、發炎反應、代謝混亂等途徑相關。而這些蛋白質將來也有望成為因聚苯乙烯微粒導致腸道損傷的潛在生物標記物,同時也為塑膠微粒致使腸道受損的毒理性提供新的見解。

    The massive release of plastic waste into the environment by humans can lead to the breakdown of these materials into smaller particles known as microplastics (MPs). These MPs can then be transferred to humans via the food chain, potentially causing biomagnification effects. Previous studies have shown that microplastics can accumulate in the gastrointestinal tract, liver, kidneys, and brain of mammals. This study used SWATH, an untargeted quantitative mass spectrometry technique, to analyze the differential proteins in the small intestine of mice exposed to polystyrene microplastics compared to a control group. The digested peptides were separated by first-dimension alkaline reversed-phase chromatography and then analyzed by nanoLC-MS/MS. Our study has maximized the size of ion database for protein identification and quantification by combining 3 fractionations and were able to identify 3666 proteins and 31501 peptides. Additionally, 2933 proteins were quantified using the SWATH method. A total of 473 proteins exhibited significant differences in expression between the experimental and control groups. Metascape analyses revealed that these differentially expressed proteins were primarily involved in cell apoptosis, inflammatory responses, , and metabolic disturbances. The study also identified several potential biomarkers for PS-MPs-induced intestinal damage. These biomarkers could be used to develop new methods for detecting and monitoring PS-MPs exposure and its health effects.

    第一章 緒論 1 第一節 前言 1 第二節 環境中的塑膠微粒 2 第三節 塑膠微粒對生物體的影響 4 第四節 塑膠微粒誘導之動物實驗對腸道的影響 6 第五節 質譜儀概述 8 第六節 電灑游離法 (Electrospray Ionization, ESI) 9 第七節 四極桿飛行時間質譜儀 (Quadrupole-Time of Flight mass spectrometry, Q-TOF) 10 第八節 掃描模式 11 一、 數據依賴採集模式 (Information/Data-dependent Acquisition, IDA/DDA) 11 二、 數據非依賴採集模式 (Data-independent Acquisition, DIA) 12 第九節 液相層析分離技術 13 一、 鹼性逆向層析法 (Alkaline reverse phase chromatography) 14 第十節 蛋白質身分鑑定 15 一、 胜肽質量指紋 (Peptide Mass Fingerprinting, PMF) 15 二、 胜肽碎片指紋 (Peptide Fragment Fingerprinting, PFF) 16 第十一節 差異蛋白質體學及其定量技術 17 一、 二維膠體電泳 (Two-Dimensional gel Eletrophoresis, 2-DE) 18 二、 化學標定 19 三、 SWATH (Sequential Window Acquisition of all Theoretical Mass Spectra) 20 第十二節 研究動機 21 第二章 實驗材料與方法 23 第一節 實驗儀器與設備 23 第二節 實驗試劑 24 第三節 小鼠試驗 25 第四節 樣品製備 27 第五節 樣品純化 27 第六節 蛋白質濃度測定 (BCA protein assay) 28 第七節 蛋白質水解 (In-solution digestion) 29 第八節 第一維分離策略 30 第九節 自製C18離心管柱去鹽 (C18 spin column) 31 第十節 奈升級超高液相層析電噴灑串聯質譜儀 (NanoLC-ESI tandem mass spectrometry) 33 一、 奈升級超高液相層析儀 (NanoAcquity UPLC system, Waters) 33 二、 四極桿飛行時間混成質譜儀 (TripleTOF 6600+ system, Sciex) 34 第十一節 數據分析 37 一、 分析軟體 37 二、 資料庫搜尋參數 37 第三章 結果與討論 39 第一節 小鼠試劑重複劑量評估 39 一、 體重變化 39 二、 血清生化 40 三、 組織病理切片 42 第二節 蛋白質樣品濃度測定 44 第三節 第一維液相分離-鹼性液相層析法 46 第四節 蛋白質鑑定及SWATH資料庫建立 47 第五節 基於SWATH方法的相對定量分析 49 第六節 生物途徑分析 52 一、 Gene Ontology 分析 52 二、 Metascape 分析 54 三、 差異蛋白質功能分析 58 第四章 結論與未來展望 64 參考文獻 65 附錄 74

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