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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 謝佳倩 | zh_TW |
| dc.contributor.advisor | Chia-Chien Hsieh | en |
| dc.contributor.author | 張琬笙 | zh_TW |
| dc.contributor.author | Wan-Sheng Chang | en |
| dc.date.accessioned | 2024-09-16T16:22:00Z | - |
| dc.date.available | 2024-09-17 | - |
| dc.date.copyright | 2024-09-16 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-13 | - |
| dc.identifier.citation | 黃沛縈 (2023)。探討Lunasin在肥胖微環境下對RAW264.7細胞與EL-4 T細胞免疫反應之影響 (為出版碩士論文)。國立臺灣師範大學，台北市。
黃靖雅 (2021)。Lunasin對C2C12肌小管細胞期發炎反應與葡萄糖利用之探討 (為出版碩士論文)。國立臺灣師範大學，台北市。 Adegunsoye, A., & Balachandran, J. (2015). Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea. Mediators of inflammation, 2015(1), 510105. Adler, K. B., Fischer, B. M., Wright, D. T., Cohn, L. A., & Becker, S. (1994). Interactions between respiratory epithelial cells and cytokines: relationships to lung inflammation. Annals of the New York Academy of Sciences, 725(1), 128-145. Akhurst, R. J. (2017). Targeting TGF-β signaling for therapeutic gain. Cold Spring Harbor perspectives in biology, 9(10), a022301. Alaswad, A. A., & Krishnan, H. B. (2016). Immunological investigation for the presence of lunasin, a chemopreventive soybean peptide, in the seeds of diverse plants. Journal of agricultural and food chemistry, 64(14), 2901-2909. Al Heialy, S., Gaudet, M., Ramakrishnan, R. K., Mogas, A., Salameh, L., Mahboub, B., & Hamid, Q. (2020). 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95774 | - |
| dc.description.abstract | 肥胖是過多能量累積造成脂肪組織增加並伴隨發炎反應，長期控制不佳者可能導致肺部纖維化。本研究欲探討在肥胖微環境下，lunasin是否能降低肺泡上皮細胞的發炎反應和纖維化的作用。本研究包含A549細胞以外加葡萄糖與棕櫚酸palmitic acid (PA)做為體外肥胖模式，與動物實驗以高油高果糖飲食誘導小鼠肥胖模式。首先在建立實驗模型的結果中，最終以7 mM正常葡萄糖與35 mM高葡萄糖 、PA 500 μM、lipopolysaccharide (LPS) 10 μg/mL和TGFβ 5 ng/mL外加入培養基中作為肥胖微環境。結果顯示，在發炎模式中，lunasin可抑制由PA或LPS誘發的低糖培養細胞之IL-6和MCP-1分泌；而低劑量的lunasin可抑制由LPS誘發高糖培養細胞之MCP-1和TGFβ分泌。在Surfactant protein (SP)的結果顯示， LPS刺激會減少正常糖培養及增加高糖培養細胞中SPD蛋白表現量，而lunasin則能夠調節其含量。分析可能作用路徑，lunasin可抑制由LPS刺激的NFκB p65的表現。在TGFβ 誘發纖維化模式中，再以刮傷癒合測定細胞遷移能力，並測量epithelial-mesenchymal transition (EMT) marker的表現，結果顯示TGFβ誘導可增加vimentin並降低E-cadherin的表現，而lunasin則無法影響TGFβ刺激後的細胞遷移與EMT表現。在肥胖小鼠實驗中，自小鼠六週大開始餵食實驗飲食，實驗分組包含正常飲食、高油高果糖飲食、腹腔注射lunasin，以及飲食添加lunasin，分析鼠肺臟組織均質液中發炎性細胞激素含量。在22週齡結果顯示，高油高果糖飲食添加lunasin可降低肺臟TNFα和TGFβ的生成。而在33週齡結果中，高油高果糖飲食的肺臟IL-6、IL-1β和IL-17a顯著降低，在腹腔注射lunasin則能提升此細胞激素生成，但飲食補充lunasin則是降低IL-6、IL-1β和TGFβ的生成。綜合上述，lunasin能夠抑制肥胖微環境下發炎肺泡中的促發炎性細胞激素IL-6、MCP-1和TGFβ分泌，且可能是透過抑制NFκB路徑的作用，但對於纖維化的影響則不顯著。未來將進一步分析，發炎與免疫防護相關的表面蛋白與其可能影響的訊息路徑。 | zh_TW |
| dc.description.abstract | Obesity is an increase in adipose tissue caused by excessive energy accumulation and is accompanied by an inflammatory reaction. Subsequently, uncontrol and long-term inflammation extends pulmonary fibrosis development. Aim of our study is to investigate whether lunasin reduces inflammation and fibrosis in A549 pulmonary epithelial cells under obese conditions. The palmitic acid (PA) and glucose were used to mimic obese conditions in vitro. The mice fed with high-fat and fructose diet were used as obese animal model. In the results of establishing the experimental model, 7 mM normal glucose and 35 mM high glucose, PA 500 μM, lipopolysaccharide (LPS) 10 μg/mL, and TGFβ 5 ng/mL were added to the culture medium as an obesity microenvironment. In inflammation, lunasin inhibited IL-6 and MCP-1 secretions induced by PA or LPS in normal glucose medium; while the low dose of lunasin inhibited MCP-1 and TGFβ secretions induced by LPS in the high glucose medium. Surfactant protein D (SP-D) executes immune response and defense. Lunasin treatment modulated SP-D levels stimulated by LPS, especially the effect was difference between normal glucose and high glucose medium. In fibrosis, the migration was determined by wound healing assay and epithelial-mesenchymal transition (EMT) marker that was stimulated by TGFβ. However, lunasin did not effect cell migration and EMT expression. In vivo, mice were divided as normal diet (ND), high-fat high-fructose diet (HF), intraperitoneal injection of lunasin (HF-IL), and dietary supplementation with lunasin (HF-DL). 33-week-old mice lung homogenate of IL-6, IL-1β, and IL-17a expression were significantly reduced in HF group, and HF-IL increased the production of these cytokines, but HF-DL group were reduced. In conclusion, lunasin inhibited cytokines IL-6, MCP-1 and TGFβ through NFκB pathway in inflamed alveoli, but this effect was not showed in fibrosis. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-09-16T16:22:00Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-09-16T16:22:00Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 中文摘要 i
英文摘要 ii 誌謝 iii 第一章 文獻探討 1 第一節 呼吸系統 1 一、 肺部中呼吸系統結構1 二、 肺泡組成 2 三、 肺表面活性劑3 四、 肺部的病理變化6 第二節 肥胖8 一、 肥胖流行病學8 二、 肥胖與免疫失調9 三、 肥胖相關的肺部疾病13 第三節 飲食因子與肺部相關研究13 一、 飲食因子對肺部環境之影響13 二、 天然物對肺部疾病之研究14 第四節 Lunasin15 一、 Lunasin簡介15 二、 Lunasin生理功效16 第五節 研究工具及模式19 一、 A549人類肺泡上皮細胞19 二、 棕櫚酸誘發之體外發炎模式19 三、 高糖誘發之體外發炎模式20 四、 TGFβ誘發之體外肺纖維化模式20 第二章 實驗動機與實驗設計22 第一節 研究動機與假說22 第二節 實驗目的23 第三節 研究架構24 第三章 實驗材料與方法25 第一節 實驗材料25 一、 實驗室儀器設備25 二、 拋棄式無菌耗材25 第二節 實驗方法26 一、 A549人類肺上皮細胞培養與藥物處理26 二、 Lunasin處理對肥胖微環境下A549細胞發炎激素及肺泡表面蛋白之影響29 三、 Lunasin處理對A549細胞遷移及其上皮細胞間質轉化之影響 31 四、 Lunasin處理對肥胖微環境下A549細胞肺泡表面蛋白及NFκB路徑表現之影響32 五、 Lunasin處理對飲食誘導的肥胖小鼠肺臟中細胞激素之影響34 六、 統計分析36 第四章 實驗結果38 第一節 建立A549細胞之體外肥胖微環境的實驗條件38 一、 葡萄糖與甘露醇處理對A549細胞存活率的影響38 二、 Lunasin、PA和TGFβ處理對A549細胞存活率的影響39 三、 在正常糖與高糖環境下PA處理對A549細胞激素分泌的影響40 第二節 Lunasin處理在肥胖微環境下對A549肺泡細胞發炎反應的影響42 一、 Lunasin處理對肥胖微環境下A549細胞其細胞激素分泌之影響42 二、 Lunasin處理對肥胖微環境下A549細胞其表面活性蛋白分泌之影響46 (一) ELISA分析46 (二) Western blot (WB) 分析46 三、 Lunasin處理對肥胖微環境下A549細胞其NFκB路徑表現之影響49 第三節 Lunasin處理在肥胖微環境下對A549肺泡細胞纖維化的影響51 一、 在高低糖環境下TGFβ處理對A549細胞存活率和細胞激素分泌的影響51 三、 上皮間質轉化標誌物螢光免疫染色57 第四節、Lunasin 介入對於餵食高油高果糖誘發肥胖小鼠肺部發炎之影響60 一、 C57BL/6小鼠在22週齡其肺臟細胞激素之分析60 二、 C57BL/6小鼠在33週齡其肺臟細胞激素之分析60 三、 C57BL/6小鼠在22週齡與33週齡其肺臟細胞激素之分析63 第五章 討論與結論64 第一節 討論64 一、 Lunasin處理在肥胖微環境下對A549肺泡細胞發炎反應的影響64 二、 Lunasin處理在肥胖微環境下對A549肺泡細胞纖維化的影響 67 三、 Lunasin介入對於飲食誘發肥胖小鼠其肺部發炎情形之影響 68 四、 肥胖微環境中體外實驗與體內實驗結果比較69 第二節 結論70 參考文獻 72 附錄96 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 探討Lunasin在肥胖微環境下對A549肺泡上皮細胞發炎反應與其可能影響機制 | zh_TW |
| dc.title | The effect of lunasin on inflammation and its possible mechanisms in A549 pulmonary epithelial cells under obese microenvironments | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林璧鳳;陳俊任;洪永瀚 | zh_TW |
| dc.contributor.oralexamcommittee | Bi-Fong Lin;Chun-Jen Chen;Yong-Han Hong | en |
| dc.subject.keyword | 肥胖,發炎,纖維化,Lunasin,肺泡上皮細胞,Surfactant protein, | zh_TW |
| dc.subject.keyword | obesity,inflammation,fibrosis,Lunasin,alveolar cell,surfactant protein, | en |
| dc.relation.page | 98 | - |
| dc.identifier.doi | 10.6342/NTU202404185 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-08-14 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | 2029-08-10 | - |
| 顯示於系所單位： | 生化科技學系 | |
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