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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳玉怜(Yuh-Lien Chen) | |
| dc.contributor.author | Wei Chang | en |
| dc.contributor.author | 張為 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:47:54Z | - |
| dc.date.available | 2025-08-17 | |
| dc.date.copyright | 2020-09-07 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78252 | - |
| dc.description.abstract | 隨著全世界工業化的興起，空氣汙染逐漸成為全球關注的公共衛生議題。空氣中的懸浮微粒(Particulate matter, PM2.5)直徑小於2.5μm，因其粒徑狹小的特性，易由肺泡之微血管進入全身循環，使得生物體內產生各種不良反應。研究顯示有害的PM2.5參與多種機制造成肺臟的危害，包括氧化壓力造成的胞毒性、氧化DNA損傷及促炎因子的刺激等等，且PM2.5增加多種呼吸道疾病的風險，包括慢性阻塞性肺疾病 (COPD)、支氣管炎、氣喘及特發性肺纖維化。在本實驗中，我們以100μg/ml的PM2.5刺激人類第二型肺泡上皮細胞 (A549細胞)，觀察細胞產生上皮間質轉換(epithelial-mesenchymal transition, EMT)之現象。實驗結果顯示，PM2.5能有效降低上皮細胞表徵E-cadherin表現，使得間質細胞表徵vimentin、TGF-β1(Transforming growth factor beta 1)及α-SMA(α-smooth muscle actin)上升，並使EMT相關轉錄因子Snail及Slug的表現上升，改變細胞形態(立方形至狹長形)並增加細胞爬行能力。此外PM2.5也會使粒線體分裂增加、細胞自噬增加以及粒線體自噬現象增加，透過加入粒線體分裂抑制劑Mdivi-1及細胞自噬抑制劑Bafilomycin A1後，可以有效降低EMT相關蛋白的表現，並降低細胞爬行能力，但加入Mdivi-1後，不影響細胞自噬及粒線體自噬之變化。而加入吡非尼酮(Pirfenidone)，一種抗纖維化藥物處理後，不論是預防或治療都可以有效降低PM2.5造成的EMT蛋白表現，並降低PM2.5造成的細胞爬行能力上升。進一步，我們以氣管內注射(intratracheal injection)方式給予小鼠PM2.5，模擬暴露空氣污染之環境。結果顯示，暴露PM2.5的小鼠其肺臟有明顯血球浸潤及肺泡壁增厚的情形，而EMT相關蛋白也有顯著改變的趨勢。給予Pirfenidone治療後，則可以有效改善此現象，並減少小鼠肺臟的膠原蛋白沉積情形。這些實驗結果證明懸浮微粒可以增加細胞粒線體分裂、細胞自噬及粒線體自噬現象，進一步導致EMT，而Pirfenidone處理可以有效降低EMT產生。 | zh_TW |
| dc.description.abstract | Environmental Particulate matter 2.5 (PM2.5) is a particle smaller than 2.5 μm which can easily penetrate deep into the respiratory tract, reach the alveolar region, participate in blood circulation because of its diameter. It is associated with the development of lung cancer, asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis and cardiovascular disease. It may also promote oxidative stress, oxidative DNA impairment and inflammation. Here, we treated human type II alveolar epithelial cells (A549 cells) with 100 μg/ml PM2.5 to study if the cells generate epithelial-mesenchymal transition (EMT). First, we demonstrated that A549 exposed to PM2.5 showed a significant decrease in epithelial marker E-cadherin, and a significant increase in mesenchymal marker vimentin, α-smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-β1). It also increased EMT-related transcriptional factors Snail and Slug, changed cell morphology from cuboid to spindle-like, and increased the ability of migration in A549. In Addition, PM2.5 promoted mitochondrial fission, autophagy and mitophagy. We can decrease expression of EMT related proteins and ability of migration through adding Mdivi-1: an inhibitor of mitochondrial fission, and Bafilomycin A1: an inhibitor of autophagy. However, Mdivi-1 did not change the expression of autophagy- and mitophagy- related proteins. Later, we treated A549 with Pirfenidone: a kind of anti-fibrosis drug and found that Pirfenidone could effectively decrease expression of EMT related proteins and PM2.5-induced migration no matter prevention or therapy. In animal model, we treated mice with PM2.5 by intratracheal injection to mimic exposing in air pollution. The lungs which treated with PM2.5 showed increased expression of EMT related proteins, and also showed blood cells infiltrated and alveolar wall thickened obviously. After treated by Pirfenidone, it could effectively improve the phenomenon and decreased collagen deposition. Taken together, these result suggested that PM2.5 could cause mitochondrial fission, autophagy and mitophagy and further leading to EMT. Giving Pirfenidone treatment could decrease the phenomenon of EMT. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:47:54Z (GMT). No. of bitstreams: 1 U0001-1208202016141600.pdf: 7883157 bytes, checksum: f9d052a868279dd78ce2d6d52487fd91 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員審定書 II 致謝 III 目錄 IV 摘要 VI Abstract VIII 壹、 緒論 1 一、 懸浮微粒與環境的關係 1 二、 懸浮微粒造成呼吸系統 (respiratory system)的危害 1 三、 懸浮微粒與上皮間質轉換 (Epithelial-Mesenchymal Transition, EMT) 之相關性 3 四、 懸浮微粒與上皮間質轉換 (EMT)的關係 5 五、 EMT與粒線體動態平衡 (mitochondrial dynamics) 的關係 6 六、 細胞自噬 (Autophagy) 7 七、 粒線體自噬 (Mitophagy) 10 八、 訊號傳遞(signal transduction) 12 九、 吡非尼酮 (Pirfenidone) 13 十、 研究動機 16 貳、 實驗材料 17 一、 儀器設備 17 二、 實驗材料與試劑 19 三、 實驗用溶液配方 24 參、 實驗方法 27 一、 PM2.5製備 27 二、 細胞培養 27 三、 細胞處理 28 四、 西方墨點法(Western blot) 28 五、 免疫螢光染色法 (Immunocytofluorescent staining, ICF stain) 33 六、 划痕測定法 (Scratch assay) 34 七、 吖啶橙螢光染色法 (Acridine orange staining, AO stain) 34 八、 動物模式 35 九、 組織石蠟包埋 (Paraffin embedding) 35 十、 蘇木精-伊紅染色法 (Hematoxylin-Eosin stain, HE staining) 36 十一、 免疫化學染色法 (Immunohistochemistry) 36 十二、 馬森三色染色法 (Masson’s trichrome staining) 37 十三、 數據統計分析 (statistical analysis) 37 肆、 實驗結果 38 一、 在PM2.5刺激下A549肺泡細胞產生EMT 38 二、 A549肺泡上皮細胞在PM2.5刺激下影響粒線體動態平衡及其與EMT的關係 39 三、 A549肺泡上皮細胞在PM2.5刺激下影響自噬作用及其與EMT的關係 40 四、 PM2.5刺激下A549肺泡細胞粒線體自噬作用之變化 42 五、 A549肺泡細胞經PM2.5刺激造成EMT之相關訊息傳遞 43 六、 PM2.5刺激下造成C57BL/6小鼠肺臟細胞產生EMT現象 44 七、 Pirfenidone有效減緩PM2.5造成細胞及小鼠肺臟之EMT現象 44 伍、 討論與結論 47 陸、 參考文獻 53 柒、 附圖 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 上皮間質轉換 | zh_TW |
| dc.subject | 細胞自噬 | zh_TW |
| dc.subject | 粒線體自噬 | zh_TW |
| dc.subject | 吡非尼酮 | zh_TW |
| dc.subject | 懸浮微粒 | zh_TW |
| dc.subject | 肺纖維化 | zh_TW |
| dc.subject | 粒線體動態平衡 | zh_TW |
| dc.subject | mitochondrial dynamics | en |
| dc.subject | lung fibrosis | en |
| dc.subject | epithelial-mesenchymal transition | en |
| dc.subject | Particulate matter | en |
| dc.subject | autophagy | en |
| dc.subject | Pirfenidone | en |
| dc.subject | mitophagy | en |
| dc.title | 探討懸浮微粒在肺臟上皮細胞對上皮間質化轉換及粒線體功能的影響 | zh_TW |
| dc.title | To study the effect of PM 2.5 on epithelial mesenchymal transition and mitochondrial function in lung epithelial cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江美治(Meei-Jyh Jiang),王懷詩(Hwai-Shi Wang),吳佳慶(Chia-Ching Wu),陳瀅(Ying Chen) | |
| dc.subject.keyword | 懸浮微粒,上皮間質轉換,肺纖維化,粒線體動態平衡,細胞自噬,粒線體自噬,吡非尼酮, | zh_TW |
| dc.subject.keyword | Particulate matter,epithelial-mesenchymal transition,lung fibrosis,mitochondrial dynamics,autophagy,mitophagy,Pirfenidone, | en |
| dc.relation.page | 92 | |
| dc.identifier.doi | 10.6342/NTU202003120 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-17 | - |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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