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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86634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 | Yi-Cheng Hsieh | en |
| dc.contributor.author | 謝宜成 | zh_TW |
| dc.date.accessioned | 2023-03-20T00:07:53Z | - |
| dc.date.copyright | 2022-08-10 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-05 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86634 | - |
| dc.description.abstract | 肝臟在人體中扮演著不可或缺的角色，其具有蛋白質合成、尿素代謝以及解毒等重要機能。隨著人們藥物濫用，飲食習慣改變等，肝纖維化乃至於肝硬化日益普及。過往的研究提出自體性物質 (例如白細胞介素-10、肝細胞生長因子等) 的補充可以逆轉肝纖維化，但效率不彰，因此如何將「自體性物質」有效地作用於肝纖維化的患部去逆轉肝纖維化是科學家亟需解決的問題。為了解決這個問題，本研究將開發一新穎的生物材料來製作肝臟貼片使被毒化後的肝臟之機能能夠回復。 本研究第一部分主要致力於肝臟貼片的製作，利用脫細胞化肝臟間質 (Decellularized liver matrix; DLM) 為基底，並於其上方修飾肝細胞生長因子 (Hepatocyte growth factor; HGF)/肝素 (Heparin) 錯合物，除了檢測該材料的性質之外，亦實際將其應用於體外藥物毒化 (CHCl3, CCl4) 後的肝細胞之回復。第二部分則首先致力於建立大鼠體內四氯化碳 (Tetracholoride; CCl4) 誘導之慢性肝纖維化模型，我們接著以第一部分所開發的肝臟貼片對於上述慢性肝纖維化之回復的影響進行檢測。本研究期許此肝臟貼片未來能實際應用於臨床治療，並為肝病治療給予新的方法與展望。 | zh_TW |
| dc.description.abstract | The liver plays an indispensable role in the human body with important functions such as protein synthesis, urea metabolism, and detoxification. However, due to drug abuse and the change of diet habit, liver fibrosis or even liver cirrhosis exists much more commonly. Previous studies show several treatments to reverse liver fibrosis by adding autologous substrates (ex. interleukin-10, hepatocyte growth factor), but with low efficiency. Thus, what the scientists heading for is the elevation of the efficiency. In order to overcome the obstacle, this study aims to develop a new biomaterial (with a few autologous substrates) to manufacture liver patch for regeneration of chemicals induced liver injury. This research is planned to be carried out within two years. In the first year, we focus on the manufacture of liver patch (hepatocyte growth factor HGF/heparin complex coating on decellularized liver matrix DLM) and the measurement of the characteristics of the material. Furthermore, we utilize liver patch to the regeneration of chemicals induced liver injury in vitro. In the second year, we commit to in vivo study inclusive of CCl4 induced liver fibrosis, then attach liver patch to fibrotic liver for reversing the fibrotic process. This study is believed to be applied in clinical applications and give us new methods and prospects for the treatment of liver disease in the near future. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-20T00:07:53Z (GMT). No. of bitstreams: 1 U0001-0208202217413400.pdf: 5236099 bytes, checksum: 84848dfede55436acb329606d4fdf1ed (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 國立臺灣大學碩士學位論文口試委員會審定書 i 誌謝 ii 摘要 iii Abstract iv 目錄 v 圖目錄 ix 表目錄 xi 第ㄧ章 前言 1 1.1 研究背景 1 1.2 研究目的 3 1.3 實驗架構 4 第二章 文獻探討 5 2.1 材料選擇 5 2.1.1脫細胞化肝臟間質 (Decellularized liver matrix; DLM) 5 2.1.2 脫細胞化技術 6 2.2 毒化物的選擇 8 2.2.1 氯仿 (CHCl3) 8 2.2.2 四氯化碳 (CCl4) 9 2.3 細胞選擇與前處理 12 成熟肝細胞 (Hepatocytes) 12 2.4 HGF 與白細胞介素 (IL-6, IL-10) 之相互關係 13 2.4.1 肝細胞生長因子 (Hepatocytes growth factor; HGF) 13 2.4.2 IL-6, IL-10 與 HGF 之交互關係 16 2.5 肝臟貼片之平台建立 17 2.5.1 過往肝纖維化之治療方式 17 2.5.2 肝素 (Heparin) 19 2.5.3 平台建立 21 2.6 肝臟貼片應用於大鼠體內實驗 22 2.6.1 Hepatic patch 過往類似地研究 22 2.6.2 格里森氏囊 (Glisson’s capsule) 23 2.6.3 腹腔給藥之藥物吸收途徑 24 2.7 明確的目標 (Specific Aims) 25 第三章 研究方法 26 3.1 實驗藥品、耗材、儀器設備與實驗動物 26 3.1.1 實驗藥品 26 3.1.2 實驗耗材 27 3.1.3 實驗儀器設備 28 3.1.4 實驗動物 29 3.2 脫細胞化肝臟間質 (DLM) 的製備 30 3.3 HGF/heparin-DLM film 的製備 31 3.4 HGF/heparin-DLM film 應用於體外實驗 33 3.4.1肝細胞毒化培養之最適化條件探討 33 3.4.2 HGF/heparin-DLM film 用於毒化後肝細胞的體外培養 34 3.5 HGF/heparin-DLM film 應用於體內實驗 35 3.5.1預防模型 (如圖十一 Prophylactic model) 35 3.5.2 治療模型 (如圖十一 Theraputic model) 35 3.6 體外實驗相關檢測方法 39 3.6.1 粒線體活性檢測 39 3.6.2 HGF, heparin 固定化濃度檢測 39 3.6.3 白蛋白 (Albumin) 活性檢測 40 3.6.4 LDH 活性檢測 40 3.6.5 尿素活性檢測 40 3.6.6 Live & Dead 螢光染色 41 3.7 體內實驗相關檢測方法 42 3.7.1 血液生化學檢驗 42 3.7.2 肝臟組織樣本採取 43 3.7.3 基因表現檢測方法 44 3.8 統計分析 46 第四章 結果與討論 47 4.1 脫細胞化肝臟間質製備結果 47 4.2 HGF/heparin-DLM film 之製作 50 4.3 DLM 對於初代肝細胞培養之影響 51 4.4 Heparin, HGF固定化結果 53 4.5 細胞毒化結果 56 4.6 細胞毒化後回復 58 4.6.1 CHCl3 毒化肝細胞後回復 58 4.6.2 CCl4 毒化肝細胞後回復 66 4.6.3 細胞毒化後回復實驗的探討 77 4.7 體內實驗 78 4.7.1 CCl4 體內誘導肝纖維化 78 4.7.2 肝臟貼片移植 80 4.7.3 血清分析 82 4.7.4 切片分析 88 4.7.5 QPCR 分析 93 4.7.6 體內實驗探討 95 第五章 結論與未來展望 96 5.1 結論 96 5.2 未來展望 98 參考資料 100 | |
| dc.language.iso | zh-TW | |
| dc.subject | 肝臟再生 | zh_TW |
| dc.subject | 四氯化碳誘導之慢性肝纖維化 (體內) | zh_TW |
| dc.subject | 四氯化碳誘導之慢性肝纖維化 (體內) | zh_TW |
| dc.subject | 四氯化碳誘導之慢性肝纖維化 (體外) | zh_TW |
| dc.subject | 四氯化碳誘導之慢性肝纖維化 (體外) | zh_TW |
| dc.subject | 氯仿誘導之慢性肝纖維化 (體外) | zh_TW |
| dc.subject | 肝細胞生長因子/肝素錯合物 | zh_TW |
| dc.subject | 脫細胞化肝臟間質 | zh_TW |
| dc.subject | 脫細胞化肝臟間質 | zh_TW |
| dc.subject | 肝細胞生長因子/肝素錯合物 | zh_TW |
| dc.subject | 肝臟再生 | zh_TW |
| dc.subject | 氯仿誘導之慢性肝纖維化 (體外) | zh_TW |
| dc.subject | Hepatocyte Growth Factor (HGF)/heparin Complex | en |
| dc.subject | Decellularized Liver Matrix (DLM) | en |
| dc.subject | CCl4 Induced Liver Fibrosis | en |
| dc.subject | Liver regeneration | en |
| dc.subject | Decellularized Liver Matrix (DLM) | en |
| dc.subject | Hepatocyte Growth Factor (HGF)/heparin Complex | en |
| dc.subject | CCl4 Induced Liver Fibrosis | en |
| dc.subject | Liver regeneration | en |
| dc.title | 肝臟貼片應用於四氯化碳毒化後之肝臟回復的研究 | zh_TW |
| dc.title | Hepatic Patch for Liver Regeneration after CCl4 Poisoning | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 倪衍玄(Yen-Hsuan Ni),黃凱文(Kai-Wen Huang),游佳欣(Jia-Shing Yu) | |
| dc.subject.keyword | 脫細胞化肝臟間質,肝細胞生長因子/肝素錯合物,氯仿誘導之慢性肝纖維化 (體外),四氯化碳誘導之慢性肝纖維化 (體外),四氯化碳誘導之慢性肝纖維化 (體內),肝臟再生, | zh_TW |
| dc.subject.keyword | Decellularized Liver Matrix (DLM),Hepatocyte Growth Factor (HGF)/heparin Complex,CCl4 Induced Liver Fibrosis,Liver regeneration, | en |
| dc.relation.page | 109 | |
| dc.identifier.doi | 10.6342/NTU202201983 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2022-08-05 | |
| 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 | 2022-08-10 | - |
| 顯示於系所單位： | 生物機電工程學系 | |
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