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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80513完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 侯詠德(Yung-Te Hou) | |
| dc.contributor.author | Yu-Chai Tai | en |
| dc.contributor.author | 戴郁儕 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:08:17Z | - |
| dc.date.available | 2023-10-31 | |
| dc.date.available | 2022-11-24T03:08:17Z | - |
| dc.date.copyright | 2021-11-04 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-29 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80513 | - |
| dc.description.abstract | " 肝纖維化 (Liver fibrosis) 為肝臟經過長期慢性損傷，使其不斷刺激細胞外基質 (Extracellular matrix, ECM) 的增生且持續堆積而導致的病變，當肝纖維化持續惡化時最終會發展為肝硬化 (Liver cirrhosis)，患者容易因肝衰竭、門脈高壓、肝性腦病等併發症而導致死亡。目前醫學上針對肝硬化有效的治療手段僅有肝臟移植而已，因此，如何在肝纖維化發展階段及早進行有效的治療便成為了避免形成肝硬化的重要議題。 CPDP 自癒合水膠是由 Chitosan-phenol (CP), Difunctionalized PEG (DP) 形成的擁有自癒合特性的水膠，在前人的研究中已經證實了 CPDP 自癒合水膠：(1) 良好的自癒合能力及可注射性；(2) 大約 0.5 kPa 與肝臟相仿的硬度；(3) 長達兩周以上的穩定降解時間。在本研究中，我們將包埋肝細胞球之 CPDP 自癒合水膠 (CPDP hydrogel-Hepatoyte spheroids, CHS) 應用於肝纖維化的回復。我們在體外實驗之結果顯示：CHS 能在五天的培養中持續生長，其相對增殖率最後達到原本的兩倍。與作為對照的包埋細胞球之膠原蛋白水膠 (Collagen hydrogel-Hepatocyte spheroids, CoHS) 相比，CHS 在培養第一天擁有顯著較高的肝蛋白合成效率，其尿素合成效率更是保持著非常顯著的高表現，證實了 CPDP 自癒合水膠作為肝細胞球載體的良好適性。另一方面，我們將 CHS 植入經四氯化碳毒化六周的大鼠纖維化肝臟，並觀察其兩周後的回復，此體內實驗之結果顯示：CPDP 自癒合水膠植入肝臟後肝細胞的凋亡有顯著的減緩，其血液 AST 值更顯著回復到一般大鼠的正常值；除此之外，CPDP 自癒合水膠對於肝機能亦有顯著的改善，其血液 Albumin 值經過兩周回復後已達到一般老鼠的正常值，而在 PAS 組織切片染色中也發現其肝醣較沒有植入水膠的肝纖維化大鼠有明顯的增加；最後，在 Picrosirius red 組織切片染色的影像分析及肝臟組織 Hydroxyproline 分析中都顯示了植入 CPDP 自癒合水膠後肝臟中細胞外基質有加速分解的趨勢，說明了肝纖維化的病變有明確的改善。另一方面，我們在 H E 組織切片染色中發現了 CPDP 自癒合水膠的植入所引起的免疫聚集現象，而植入 CHS 的肝纖維化大鼠在血液 ALT, AST 值的升高亦暗示了其中包埋的肝細胞球可能已經死亡。然而，我們同時也在植入 CHS 一周後觀察到血液中的 Albumin 較僅植入水膠的組別有所提升，顯示肝細胞球在植入後對肝機能帶來的正面效益，符合我們在體外實驗中所發現的趨勢。 我們在本研究中充分展現了 CPDP 自癒合水膠在抑制細胞凋亡、肝臟合成功能提升以及纖維化肝臟中促進細胞外基質之分解等面向的顯著改善，CPDP 自癒合水膠不但具有讓肝纖維化恢復的功效、亦有作為肝細胞球載體的臨床應用潛力。未來我們將致力於：(1) 透過免疫反應的調控來更加真實、具體的呈現 CPDP 自癒合水膠以及肝細胞球對於肝纖維化回復的影響，並且研究其在肝臟回復過程中所扮演的角色；(2) 透過加入肝臟脫細胞基質 (Decellularized liver matrix, DLM) 來更進一步改善 CPDP 自癒合水膠的微環境 (Microenvironment)。我們相信 CPDP 自癒合水膠於未來肝臟組織工程中的應用能夠有更一步的拓展，充分發揮其作為生醫材料的潛力及價值。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:08:17Z (GMT). No. of bitstreams: 1 U0001-2710202104330600.pdf: 3688297 bytes, checksum: 94d0799b7a900d71318234d9ba08e447 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 摘要 i Abstract iii 目錄 iv 圖目錄 viii 表目錄 x 第一章 前言 1 1.1 研究目的 1 1.2 實驗架構 2 第二章 文獻探討 4 2.1 自癒合水膠 (Self-healing hydrogel) 4 2.2.1 CPDP 自癒合水膠 4 2.2 肝臟組織工程 7 2.2.1 肝細胞 (Hepatocytes) 8 2.2.2 肝細胞球 (Hepatocyte spheroids) 8 2.3 肝纖維化 (Liver fibrosis) 10 2.4 綜合深入探討 13 第三章 研究方法 15 3.1 實驗藥品、耗材、儀器設備與實驗動物 15 3.1.1 實驗藥品 15 3.1.2 實驗耗材 16 3.1.3 實驗儀器設備 17 3.1.4 實驗動物 17 3.2 CPDP 自癒合水膠製備 18 3.2.1 Chitosan-phenol 製備 18 3.2.2 Difunctionalized PEG 製備 18 3.3 大鼠初代肝細胞採取 19 3.4 肝細胞球的培養 19 3.4.1 MPC dish 製備 19 3.4.2 MPC dish 應用於肝細胞培養 20 3.4.3 肝細胞球粒徑分析 (Particle analysis) 20 3.5 含細胞源之水膠的形成 21 3.5.1 含肝細胞/肝細胞球之 CPDP 自癒合水膠的形成 21 3.5.2 含肝細胞球之膠原蛋白水膠的形成 21 3.6 體外實驗與相關檢測方法 22 3.6.1 體外實驗設計 22 3.6.2 相對增殖率檢測 24 3.6.3 肝蛋白 (Albumin) 合成量檢測 24 3.6.4 尿素 (Urea) 合成量檢測 26 3.7 體內實驗以及相關檢測方法 27 3.7.1 體內實驗設計 27 3.7.2 大鼠的肝纖維化模型 29 3.7.3 CPDP 自癒合水膠的植入 29 3.7.4 血液生化學檢驗 30 3.7.5 肝臟組織樣本採取 31 3.7.6 Hydroxyproline 分析 32 3.7.7 肝臟組織切片與染色 33 3.7.7.1 組織切片脫蠟復水 33 3.7.7.2 Hematoxylin and Eosin (H E) 染色 33 3.7.7.3 Periodic Acid Schiff (PAS) 染色 34 3.7.7.4 Picrosirius red 染色 34 3.7.8 纖維化區域影像分析 35 3.8 基因表現檢測方法 36 3.8.1 RNA的萃取 36 3.8.1.1 組織細胞溶解 36 3.7.7.1 RNA的純化 36 3.8.2 RNA的溶解與分析 37 3.8.3 Complementary DNA (cDNA) 合成 37 3.8.4 Quantitative polymerase chain reaction (qPCR) 37 3.9 統計分析 (Statistical analysis) 38 第四章 結果與討論 39 4.1 肝細胞球的培養 39 4.2 CPDP 自癒合水膠體外實驗結果 41 4.2.1 相對增殖率檢測 41 4.2.2 肝蛋白 (Albumin) 合成效率檢測 43 4.2.3 尿素 (Urea) 合成效率檢測 45 4.2.4 體外實驗總結 46 4.3 CPDP 自癒合水膠體內實驗結果 48 4.3.1 血液生化學 48 4.3.2 Hydroxyproline 分析 51 4.3.3 組織切片染色分析 53 4.3.3.1 H E 組織切片染色結果 53 4.3.3.2 PAS 組織切片染色結果 55 4.3.3.3 Picrosirius red 組織切片染色結果 57 4.3.4 相對基因表現分析 60 4.3.5 體內實驗總結 62 第五章 結論與未來展望 64 5.1 結論 64 5.2 未來展望 66 參考資料 67 參考文獻 67 | |
| dc.language.iso | zh-TW | |
| dc.subject | 肝細胞球 | zh_TW |
| dc.subject | 自癒合 | zh_TW |
| dc.subject | 甲殼素 | zh_TW |
| dc.subject | 水凝膠 | zh_TW |
| dc.subject | 肝纖維化 | zh_TW |
| dc.subject | Hydrogel | en |
| dc.subject | Liver fibrosis | en |
| dc.subject | Self-healing | en |
| dc.subject | Chitosan | en |
| dc.subject | Hepatocyte spheroids | en |
| dc.title | 以甲殼素為基底之自癒合水膠應用於肝纖維化的回復 | zh_TW |
| dc.title | "Self-healing, chitosan-based hydrogel for the regeneration of liver fibrosis" | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 徐善慧(Hsin-Tsai Liu),陳彥榮(Chih-Yang Tseng) | |
| dc.subject.keyword | 自癒合,甲殼素,水凝膠,肝纖維化,肝細胞球, | zh_TW |
| dc.subject.keyword | Self-healing,Chitosan,Hydrogel,Liver fibrosis,Hepatocyte spheroids, | en |
| dc.relation.page | 72 | |
| dc.identifier.doi | 10.6342/NTU202104299 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-29 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 生物機電工程學系 | zh_TW |
| dc.date.embargo-lift | 2023-10-31 | - |
| 顯示於系所單位： | 生物機電工程學系 | |
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