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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 林淑華(Shu-Wha Lin) | |
| dc.contributor.author | Guan-Ren Wang | en |
| dc.contributor.author | 王冠人 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:16:11Z | - |
| dc.date.available | 2021-11-03 | |
| dc.date.available | 2022-11-24T03:16:11Z | - |
| dc.date.copyright | 2021-11-03 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80776 | - |
| dc.description.abstract | "絲胺酸蛋白酶(serine protease) 在生物體中扮演著非常重要的角色，也與許多小鼠及人類疾病的病因有關。其中第二型穿膜絲胺酸蛋白酶 (Type II transmembrane serine proteases, TTSP) 的缺失與小鼠及人類的發育疾病都有關聯。 Hepsin屬於TTSP，主要表現在肝臟，少量表現在其他組織，但對其發育相當重要，例如Hepsin會調控脂肪細胞分化、胚胎耳蝸的發育以及胚胎著床等。先前本實驗室利用Hepsin基因改造小鼠探討絲胺酸蛋白酶與小鼠橫膈膜發育的相關性，發現 Hepsin基因剔除(Hepsin-/-)小鼠肺功能較野生型小鼠(Hepsin+/+) 差，且Hepsin-/-成鼠肝臟末緣至肋骨最後一節距離較小，上述表徵類似橫膈上提(diaphragmatic eventration) 的病理現象，此外Hepsin-/-成鼠橫膈膜也較小，橫膈膜病理切片也發現中央肌腱 (central tendon) 區域較薄。進一步對胚胎橫膈膜發育進行研究，以切片染色分析小鼠E13.5胚胎時發現Hepsin -/-胚胎橫膈膜前驅結構(pleuroperitoneal fold, PPF)面積、肌肉前驅細胞(muscle precursor cell)及纖維母細胞(fibroblast) 的細胞計數皆無變化。 為了釐清先前成鼠與胚胎結果的差異性，本研究首先利用回交C57BL/6Jnarl 超過10代以上之6-8週齡成鼠作分析Hepsin各基因型小鼠之肝臟末端至肋骨末緣之距離，發現無論公鼠或母鼠，Hepsin -/-成鼠肝臟末緣至肋骨最後一節距離較異合型(Hepsin+/-) 成鼠與Hepsin+/+成鼠小，也有類似橫膈上提的情形。進一步測量橫膈膜的直徑與面積，觀察到無論公鼠或母鼠，Hepsin -/- 成鼠橫膈膜的直徑與面積皆較小。此外，無論公鼠或母鼠，Hepsin -/- 成鼠其橫膈膜肌肉層無變化，但中央肌腱層皆明顯較薄。接著分析E13.5小鼠胚胎，利用切片H E染色，量測其PPF面積，發現Hepsin -/- 小鼠胚胎PPF面積明顯小於Hepsin+/+與Hepsin+/- 小鼠胚胎PPF面積。進一步對E13.5小鼠胚胎進行切片免疫螢光染色，計數每個切片所有PPF中的PAX7 (肌肉前驅細胞)陽性細胞與GATA4 (纖維母細胞)陽性細胞，結果顯示Hepsin -/-小鼠胚胎其纖維母細胞無變化，但肌肉前驅細胞明顯較少。接著測量E13.5胚胎整體橫膈膜直徑及面積，結果發現無論在胚胎橫膈膜直徑橫向、縱向與面積，三種Hepsin基因型小鼠(Hepsin -/-、Hepsin+/+與Hepsin+/-)間皆無明顯差異。以肌腱前驅細胞(tendon precursor cell)的標誌性蛋白mouse Scleraxis (mSCX) 的RNA作為探針利用全標本包埋原位雜合技術(whole mount in situ hybridization, WISH)，偵測E13.5胚胎橫膈膜肌腱的型態與含量，結果發現E13.5胚胎橫膈膜，三種Hepsin基因型小鼠(Hepsin -/-、Hepsin+/+與Hepsin+/-)間皆無明顯差異。 綜合上述結果，推測Hepsin 缺失可能造成小鼠橫膈膜發育異常，並且Hepsin 可能透過影響肌肉前驅細胞，進而影響橫膈膜中央肌腱的發育，造成類似橫膈上提的病理現象。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:16:11Z (GMT). No. of bitstreams: 1 U0001-1110202117425400.pdf: 4188459 bytes, checksum: 54ad4106704d8877d5b364f953a30cbe (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定書 ii 致謝 iii 中文摘要 iv 英文摘要 vi 目錄 viii 圖目錄 x 表目錄 xi 第一章、緒論 1 前言 1 第二型穿膜絲胺酸蛋白酶 1 缺乏第二型穿膜絲胺酸蛋白酶的相關發育問題 2 Hepsin的組織分布與蛋白結構 2 Hepsin功能探討 3 橫膈膜的功能與結構 4 橫隔膜的發育 5 橫膈膜疝氣 (diaphragmatic hernia) 7 橫膈上提 (diaphragmatic eventration) 7 橫膈膜缺陷相關機制 8 研究目的 11 第二章、材料與方法 12 小鼠實驗 12 實驗動物犧牲與石蠟切片製作 12 小鼠橫膈膜解剖及型態觀察 12 組織染色(Hematoxylin and Eosin stain) 13 免疫組織螢光染色(Immunofluorescence, IF) 13 PPF面積計算 14 PPF中肌肉前驅細胞與纖維母細胞計數 15 胚胎橫膈膜解剖及型態觀察 15 mSCX DNA轉殖片段製備 16 全標本包埋原位雜合（Whole mount in situ hybridization, WISH）實驗用之mSCX RNA探針製備 16 全標本包埋原位雜合（Whole mount in situ hybridization, WISH） 17 數據分析與統計 18 第三章、實驗結果 19 Hepsin-/-成鼠肝臟末端至肋骨末緣之距離明顯較小 19 Hepsin-/-成鼠橫向、縱向距離與橫膈膜面積明顯較小 19 Hepsin-/-成鼠橫膈膜中央肌腱組織厚度較薄 20 Hepsin-/- E13.5 胚胎PPF面積較小 21 Hepsin-/- E13.5 胚胎PPF中肌肉前驅細胞較少 21 Hepsin-/- E13.5 胚胎橫膈膜大小正常 21 以WISH探討肌腱前驅細胞相關轉錄因子mSCX 22 第四章、討論 24 Hepsin-/- 成鼠橫膈膜發育異常 24 Hepsin-/- E13.5胚胎PPF面積較小且PPF中肌肉前驅細胞數量較少 25 Hepsin-/- E13.5 胚胎橫膈膜與 Hepsin+/+ E13.5 胚胎橫膈膜無異 26 全標本包埋原位雜合需累積實驗數據並改善實驗流程 27 綜合本篇論文與先前實驗室成果比較及綜合討論 29 未來實驗規劃 32 參考文獻 33 圖 41 表 62 附錄 64" | |
| dc.language.iso | zh-TW | |
| dc.subject | 橫膈上提 | zh_TW |
| dc.subject | 橫膈膜發育 | zh_TW |
| dc.subject | pleuroperitoneal fold | zh_TW |
| dc.subject | whole mount in situ hybridization | zh_TW |
| dc.subject | Hepsin基因剔除小鼠 | zh_TW |
| dc.subject | whole mount in situ hybridization | en |
| dc.subject | Hepsin knockout mice | en |
| dc.subject | diaphragm development | en |
| dc.subject | diaphragm eventration | en |
| dc.subject | pleuroperitoneal fold | en |
| dc.title | 利用基因改造小鼠探討絲胺酸蛋白酶與小鼠橫膈膜發育的相關性 | zh_TW |
| dc.title | Investigating the role of serine proteases in relation to murine diaphragm development using genetically modified mouse model | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳瑞菁(Hsin-Tsai Liu),黃祥博(Chih-Yang Tseng),游益興 | |
| dc.subject.keyword | Hepsin基因剔除小鼠,橫膈膜發育,橫膈上提,pleuroperitoneal fold,whole mount in situ hybridization, | zh_TW |
| dc.subject.keyword | Hepsin knockout mice,diaphragm development,diaphragm eventration,pleuroperitoneal fold,whole mount in situ hybridization, | en |
| dc.relation.page | 68 | |
| dc.identifier.doi | 10.6342/NTU202103654 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| Appears in Collections: | 醫學檢驗暨生物技術學系 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| U0001-1110202117425400.pdf Access limited in NTU ip range | 4.09 MB | Adobe PDF |
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