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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林峯輝 | zh_TW |
| dc.contributor.advisor | Feng-Huei Lin | en |
| dc.contributor.author | 袁苙芸 | zh_TW |
| dc.contributor.author | Li-Yun Yuan | en |
| dc.date.accessioned | 2023-05-05T17:33:49Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-05-05 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2022-12-07 | - |
| dc.identifier.citation | 1. Foster-Goldman, A. and D. McCarthy, Angioedema from recombinant TPA administration: case report and pathophysiology review. American journal of therapeutics, 2013. 20(6): p. 691-693.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87109 | - |
| dc.description.abstract | 腦中風是指腦部發生急性的血管病變，而本研究所探討之缺血性腦中風佔了 所有中風的 87%，是由於腦部因血栓阻塞而造成局部血液循環不足、供氧減少而 對細胞產生傷害。而病人常因為中風後留下的嚴重後遺症，造成長期失能，因此 在急性期給予病人有效的治療，減少因為中風而造成的神經學症狀是一個相當重 要的議題，而現今臨床診療指引所提供的靜脈血栓溶解治療及血管內取栓術，則 因為適應症規範嚴格，少有患者能使用，意即現行治療只在腦中風初期直接注射 讓血栓溶解的藥物，而後就沒有其他介入治療方式。
因此本研究開發一個材料作為一個藥物載體，利用膠體測試不同中風階段的 有效藥物，輔助臨床研究進而找到適合的藥物。本研究主要聚焦於在腦組織受傷 前期，藉由降低發炎反應幫助後面神經功能的傷後組織功能恢復更容易形成。將 設計溫感型透明質酸(HA)膠體搭載藥物藉由硬腦膜下腔注射填入中風的空腔， 而搭載的藥物則具有抗發炎、抗氧化、組織修復和再生能力的表沒食子兒茶素沒 食子酸酯(EGCG)。 本研究以 FTIR 和 1H-NMR 檢驗交聯官能基的改變與交聯程度，再鑑定膠體 流變性質以及模擬體外降解，測定降解速率，以及體外藥物釋放速率;細胞實驗 的部分，使用 WST-1 測定細胞材料毒性，Live/Dead 染色觀察細胞活性;動物實 驗，利用光栓塞(photothrombosis stroke)造成小鼠產生缺血性中風並注入本實驗之 溫感型膠。最後，行為實驗及組織切片分析，顯示本實驗材料 HXP 確實可以於 動物模型中風後初期階段搭載 EGCG 藥物注射至中風空腔，且可加速組織修復。 | zh_TW |
| dc.description.abstract | Stroke is one of the leading causes of mortality and disability worldwide. This study focuses on ischemic stroke, which accounts for about 87 % of all strokes. Ischemic stroke happens when a vessel supplying blood to the brain is obstructed. Considered the clinical guideline, tissue plasminogen activator, tPA, is the gold standard for treating ischemic stroke. However, many people couldn’t meet the indication criterias to receive the medication. Besides, current treatment only focuses on dissolving the clot in the early stage of stroke onset; there is no other following treatment to facilitate the tissue-repairing process. To assist current clinical research, we develop a hyaluronate-based thermosensitive gel, “HXP” for decreasing the initial inflammatory response, facilitating the following proliferation and remodeling process in the early stage of ischemic stroke. We expected to minimize the stress and death of the tissue around the stroke site and reduce the inflammatory response.
We used FTIR and 'H-NMR to ensure the cross-linking reaction between Pluronic F127and HA. We also measured rheological properties, release profile and degradation rate of our materials. For the in vitro study, WST-1 assay and Live/Dead staining were used to test cytotoxicity and biocompatibility. For the in vivo study, we conducted photothrombotic stroke on mice to induce ischemic stroke. In sum, EGCG-loaded HXP was found to be effective in mice behavioral tests and histology analysis. Also, HXP gel exhibits the potential to help the clinical study of different stages in acute ischemic stroke. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-05T17:33:49Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-05-05T17:33:49Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 ...i
誌謝 ...ii 中文摘要 ... iii Abstract...iv 目錄 ...v 圖目錄 ...ix 表目錄 ...xiii 公式目錄 ...xiv 名詞縮寫目錄 ...xv 第一章 緒論 ...1 1.1 前言...1 1.2 腦中風的定義與分類 ...1 1.2.1 缺血性中風 ...2 1.2.2 出血性中風 ...3 1.3 腦中風之後遺症 ...4 1.4 腦中風之流行病學及疾病負擔 ...4 1.4.1 腦中風之流行病學 ...4 1.4.2 經濟影響 ...7 1.5 缺血性腦中風的治療方法 ...7 1.5.1 靜脈注射血栓溶解劑(Tissue plasminogen activator，tPA) ...7 1.5.2 血管內取栓術(Endovascular thrombectomy) ....8 1.5.4 藥物治療 ...9 1.6 研究目的 ...10 第二章 文獻回顧 ...12 2.1 光栓塞中風模型 (Photothrombosis stroke, PT stroke) ...12 2.2 材料選擇 ...14 2.2.1 表沒食子兒茶素沒食子酸酯(Epigallocatechin gallate, EGCG) ...14 2.2.2 透明質酸(HA) ...16 2.2.3 普朗尼克(Pluronic F127, PF 127) ...17 2.2.4 透明質酸(HA)與普朗尼克(Pluronic F127)交聯 ...18 第三章 材料與方法 ...19 3.1 實驗藥品 ...19 3.2 實驗儀器 ...20 3.3 實驗架構 ...21 3.4 材料製備與分析 ...22 3.4.1 製備交聯透明質酸混合兒茶素 ...22 3.4.2 傅里葉轉換紅外光譜(Fourier-transform Infrared, FTIR) ...23 3.4.3 核磁共振光譜(Nuclear magnetic resonance spectroscopy, NMR) ...23 3.4.4 流變儀(Rheometer) ...23 3.4.5 降解速率測試(Degradation test) ...24 3.4.6 藥物釋放(Drug release profile) ...24 3.5 體外實驗(In vitro study) ...25 3.5.1 細胞株與培養液 ...25 3.5.2 WST-1 細胞活性測試(Water Soluble Tetrazolium Salt-1, WST-1) ...25 3.5.3 細胞毒性測試(Live & Dead Staining) ...26 3.6 動物實驗(In vivo) ...28 3.6.1 實驗動物與組別設計 ...28 3.6.2 光栓塞模型(Photothrombosis model) ...30 3.6.3 染劑擴散實驗(Dye diffusion test) ...30 3.6.4 行為測試( Behavioral test ) ...31 3.6.5 組織染色分析(Histology) ...32 3.6.6 酵素免疫分析 (ELISA) ...33 3.7 統計分析與方法(Statistic method) ...35 第四章 結果與討論 ...36 4.1 材料分析 ...36 4.1.1 傅里葉轉換紅外光譜分析(Fourier-transform infrared, FTIR) ...36 4.1.2 核磁共振光譜(Nuclear magnetic resonance spectroscopy, NMR) ... 37 4.1.3 流變特性檢測 (Rheological Properties) ...37 4.1.4 降解速率測試 (Degradation test) ...38 4.1.5 藥物釋放測試 (Drug Release Profile) ...39 4.2 細胞實驗(In vitro study) ...39 4.2.1 WST-1 細胞活性測試( Water Soluble Tetrazolium Salt-1, WST-1) .39 4.2.2 細胞毒性測試(Live & Dead Staining) ...40 4.3 動物實驗(In vivo study) ...41 4.3.1 建立光栓塞模型(Photothrombosis Model) ...41 4.3.2 染劑擴散實驗(Dye diffusion test) ...42 4.3.3 行為測試-轉角測驗(Behavioral test – Corner turning test) ...43 4.3.4 行為測試-步態分析(Behavioral test – Catwalk analysis) ...44 4.3.4 組織染色分析 (Histology) ...47 4.3.5 酵素免疫分析 (ELISA) ...52 第五章 結論 ...55 第六章 未來展望 ...56 參考文獻 ... 57 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 以溫感型透明質酸膠體作為控制藥物釋放載體評估急性缺血性腦中風之保護潛力 | zh_TW |
| dc.title | The Preparation and Evaluation of Hyaluronate-Based Thermosensitive Gel Loaded with EGCG in Early Stage of Acute Ischemic Stroke | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 蕭名彥 | zh_TW |
| dc.contributor.coadvisor | Ming-Yen Hsiao | en |
| dc.contributor.oralexamcommittee | 郭士民;陳克紹 | zh_TW |
| dc.contributor.oralexamcommittee | Shyh-Ming Kuo;Ko-Shao Chen | en |
| dc.subject.keyword | 透明質酸,溫感型膠體,光栓塞中風,缺血性中風, | zh_TW |
| dc.subject.keyword | HA,thermosensitive gel,photothrombotic stroke,ischemic stroke, | en |
| dc.relation.page | 61 | - |
| dc.identifier.doi | 10.6342/NTU202210084 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2022-12-08 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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