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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52319完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余佳慧(Linda Chia-Hui Yu) | |
| dc.contributor.author | Wei-Wun Liu | en |
| dc.contributor.author | 劉韋妏 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:11:46Z | - |
| dc.date.available | 2020-09-25 | |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-18 | |
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Induction of TrkB by retinoic acid mediates biologic responsiveness to BDNF and differentiation of human neuroblastoma cells. Eukaryotic Signal Transduction Group. Neuron 1993;11:321-31. 196. Ross RA, Spengler BA, Biedler JL. Coordinate morphological and biochemical interconversion of human neuroblastoma cells. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52319 | - |
| dc.description.abstract | 背景:腸躁症(Irritable bowel syndrome)是一種常見的功能性腸胃道失調疾病，特徵為長期反覆性腹痛和排便習慣的改變，卻無特定病因或病原菌的存在。近期研究發現，血清素（serotonin, 5-hydroxytryptamine, 5-HT）、膽囊收縮素(cholecystokinin;CCK)、神經生長因子(nerve growh factor;NGF)與腸道痛覺敏感有其相關性。然而，腸躁症與其內臟痛覺敏感的病理機制仍不明。因此，我們實驗室利用人類母細胞瘤SH-SY5Y細胞探討CCK是否導致神經纖維延長，並利用後感染及精神壓力之雙重刺激因子來建立腸道痛覺敏感之小鼠模式和評估血清素受器配體對內臟高敏感性和腸道功能的影響。 方法:細胞實驗部分，利用人類SH-SY5Y神經母細胞株加入視黃酸(retinoic acid;RA)促使分化後，給予硫酸化的CCK-8S (sulphated CCK octapeptide)培養，而後測量其神經纖維長度，觀察神經纖維生長變化。動物實驗部分，利用後感染及精神壓力雙重因子的小鼠，測試血清素受器配體對其內臟敏感與腸胃道蠕動狀況的影響。藉由內臟動器對結直腸撐張來評估腹痛敏感程度。 結果:神經母細胞經RA作用分化後給予CCK-8S作用，結果神經纖維生長為3倍。若預先給予中和性anti-NGF或 CCK-A 或CCK-B receptor inhibitors (AIH或BIH)均能顯著降低神經纖維的延長。透過西方轉漬法分析發現，經CCK-8S作用後的神經細胞，其NGF蛋白的表現量會提高。此外，血清素受器配體不論以腹腔注射（單次性）或經口給予（單次或連續性），皆可有效降低小鼠的內臟敏感性，但惟有連續性經口給予可以減緩腸胃道蠕動。 結論:本篇細胞實驗證實了，CCK-8S能促使神經纖維的延長，藉由結合至CCK受器以及增加NGF的表現來達成。此外，血清素受器配體能降低小鼠的內臟敏感性。因此推論，CCK和5-HT有參與腸道痛覺高敏感性之機制。 | zh_TW |
| dc.description.abstract | Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic recurrent abdominal pain and altered bowel habits, in the absence of identifiable organic cause and macroscopic lesions. Recent findings indicate links between serotonin (5-hydroxytryptamine, 5-HT), cholecystokinin (CCK) and nerve growth factor (NGF) with intestinal hyperalgesia. However, the mechanism of visceral hypersensitivity in IBS remains unclear. The aim is to evaluate whether CCK may cause neurite outgrowth in human neuroblastoma SH-SY5Y cells and the effecst of 5-HT7 receptor ligand on visceral hypersensitivity and gut dysfunctions in a mouse model of dual triggers of post-infection and psychological stress. Method: SH-SY5Y cells were treated with retinoic acid (RA) to induce cell differentiation, and then cultured with sulphated CCK octapeptide (CCK-8S) for measurement of nerve fiber length. In some experiments, 5-HT7 receptor ligands were intraperitoneally administered to mice with dual triggers of post-infection and psychological stress. Abdominal pain was evaluated by visceromoter response to colorectal distension. Result: SH-SY5Y cells displayed 3-times increase of nerve fiber length after incubation with exogenously CCK-8S compared to control group. Moreover, pretreatment with neutralizing anti-NGF or with antagonists to CCK receptors decreased the nerve fiber length in cells incubated with CCK-8S. Western blots showed increased level of NGF in cells after culturing with CCK-8S. In addition, intraperitoneal (one dose) and peroral (one or multiple doses) administration of 5HT7 receptor ligands inhibited visceral hypersensitivity; however, only multiple peroral dose reduced intestinal motility. Conclusion: Exogenously CCK-8S induces neurite outgrowth via CCK receptors and induction of NGF synthesis. Moreover, 5HT7 receptor ligands inhibited visceral hypersensitivity. In sum, CCK and 5-HT are involved in the mechanisms of intestinal hyperalgesia. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:11:46Z (GMT). No. of bitstreams: 1 ntu-104-R02441011-1.pdf: 1838459 bytes, checksum: 46bc6cf53df5f4aa89b013708afb08e6 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 致謝 I 摘要 II Abstract III 目 錄 IV 圖目錄 VII 一、前言 1 1 腸道結構與功能 1 2 腦腸軸 (Brain-gut axis, BGA) 1 3 內臟痛覺傳遞 (Visceral pain pathways) 3 3.1 上行痛覺調控路徑 (Ascending visceral pain pathway) 3 3.2 下行痛覺調控路徑 (Descending visceral pain pathway) 4 3.3 內臟高敏感性 (Visceral hypersensitivity) 4 4 腸躁症 (Irritable bowel symdrom, IBS) 5 4.1 流行病學研究 5 4.2 臨床研究 6 4.3 風險因子 7 4.3.1 精神壓力 7 4.3.2 腸胃道感染 9 4.3.3 梨形鞭毛蟲感染與後感染腸躁症 (Postinfectious irritable bowel syndrome, PI-IBS) 10 4.3.4 動物模式之建立 12 5 腸道疼痛相關的神經激素(neuroendocrine)和其他介質(mediators) 13 5.1 血清素 (Serotonin) 13 5.2 膽囊收縮素(Cholecystokinin, CCK) 14 5.3 下視丘─腦下垂體─腎上腺皮質軸與腎上腺皮質酮 (Hypothalamic- pituitary-adrenal axis, HPA axis and corticosterone) 18 5.4 肥大細胞 (Mast cells) : 組織胺(histamine)與蛋白酶 (protease) 19 6 腸躁症痛覺敏感化與神經細胞功能型態之間的關聯性 20 6.1 神經細胞興奮性的提升 20 6.2 痛覺受器表現量的改變 20 6.3 神經纖維的延長 22 6.4 神經營養因子 (Neurotrophins) 22 6.5 人類神經母細胞瘤 SH-SY5Y 細胞株作神經分化和纖維生長的模式 …………………………………………………………………….…24 7 研究目的 25 二、材料與方法 26 1 實驗動物 26 2 實驗寄生蟲Giardia lamblia感染模式 26 2.1 動物感染方法 27 2.2 梨形蟲滋養體 (Giardia lamblia trophozoites) 計數 27 3 動物精神壓力模式 27 4 血清素受體拮抗劑（serotonin/5-HT receptor antagonist） 28 5 實驗動物分組與流程 28 5.1 梨形蟲感染與避水壓力實驗 28 5.2 拮抗劑試驗 29 6 細胞試驗 30 6.1 使用細胞株 30 6.2 神經纖維生長(neurite outgrowth)實驗 30 6.3 細胞影像的擷取與神經細胞纖維長度測量 31 6.4 細胞實驗使用之中和性抗體和拮抗劑 32 6.4.1 Neutralizing anti-NGF 32 6.4.2 CCK receptor inhibitors 32 7 組織處理與實驗分析小鼠體重 (body weight) 分析 32 8 內臟動器反應（visceromotor response, VMR）分析 32 9 腸胃道蠕動測試之活性碳飲食試驗(charcoal meal test) 34 10 組織切片與染色 34 10.1 冷凍包埋檢體製備 34 10.2 免疫螢光染色(Immunofluorescence；IF) 34 10.3 石蠟包埋檢體製備 35 10.4 免疫染色 (Immunohistochemistry；IHC) 35 11 西方轉漬法 （western blotting） 36 11.1 蛋白質萃取 36 11.2 蛋白質電泳 37 11.3 蛋白質分析 37 11.4 抗體列表 38 (1) IF or IHC 38 (2) 西方轉漬法所用抗體 38 (3) 中和用抗體 38 (4) 二級抗體 38 12 統計方法 39 三、實驗結果 40 1 SH-SY5Y神經母細胞經RA及CCK-8S刺激之神經纖維長度變化 40 1.1 RA處理分化後的神經纖維長度 40 1.2 CCK-8S劑量時間效應(dose-time response)實驗 40 2 神經營養因子對CCK-8S刺激引起SH-SY5Y神經纖維長度的影響 41 3 探討CCK受器拮抗劑處理對SH-SY5Y神經纖維長度的影響 42 4 探討CCK-8S刺激後SH-SY5Y神經細胞的NGF表現量 42 5 小鼠腸道痛覺敏感異常之機制研究 42 5.1 小鼠內臟動器反應和腸轉運百分比 42 5.2 腹腔注射受器配體對小鼠腸道內臟敏感性及腸胃蠕動的影響 44 5.3 經口給予受器配體對小鼠腸道內臟敏感性及腸胃蠕動之影響 44 5.4 連續十天經口給予受器配體之小鼠腸道內臟敏感性及腸胃蠕動狀況 ……………………………………………………….………………45 5.5 比較經口給予受器配體和拮抗劑之小鼠腸道內臟敏感性及腸胃蠕動狀況 46 四、討論 47 參考文獻 76 圖表目錄 表一、小鼠腸道外觀和組織異常狀態觀察與統計 56 圖一、SH-SY5Y 細胞生長型態 58 圖二、多次性給予CCK-8S對神經纖維長度的劑量時間效應 59 圖三、一次性給予CCK-8S對神經纖維長度的劑量時間效應 60 圖四、中和性抗體anti-NGF對CCK-8S培養之SH-SY5Y神經細胞纖維長度之影響 61 圖五、CCK受體拮抗劑對CCK-8S培養之SH-SY5Y神經細胞纖維長度之影響 62 圖六、CCK-8S處理之SH-SY5Y神經細胞中NGF的表現量 63 圖七、PN小鼠與GW小鼠之內臟痛覺反應及腸胃蠕動狀況 64 圖八、5HT-7受器表現量 65 圖九、大腸組織5HT免疫染色 66 圖十、腹腔注射受器配體之PN和GW小鼠腸道內臟敏感性 67 圖十一、腹腔注射受器配體對GW小鼠腸道內臟敏感性及腸胃蠕動的影響 68 圖十二、經口給予受器配體對GW小鼠腸道內臟敏感性及腸胃蠕動之影響 69 圖十三、不同時間經口給予受器配體對GW小鼠腸道內臟敏感性及腸胃蠕動之影響 70 圖十四、連續十天經口給予受器配體之GW小鼠腸道內臟敏感性及腸胃蠕動狀況 71 圖十五、比較經口給予受器配體或拮抗劑之GW小鼠腸道內臟敏感性及腸胃蠕動狀況 72 圖十六、經口給予受器配體或拮抗劑之GW小鼠腸道外觀狀態 73 圖十七、經口給予受器配體或拮抗劑之GW小鼠腸道組織H E染色結果 74 | |
| dc.language.iso | zh-TW | |
| dc.subject | 神經纖維生長 | zh_TW |
| dc.subject | 內臟高敏感性 | zh_TW |
| dc.subject | 腸躁症 | zh_TW |
| dc.subject | 精神壓力 | zh_TW |
| dc.subject | 梨形蟲 | zh_TW |
| dc.subject | visceral hypersensitivity | en |
| dc.subject | irritable bowel syndrome | en |
| dc.subject | psychological stress | en |
| dc.subject | Giardia lamblia | en |
| dc.subject | neurite outgrowth | en |
| dc.title | 腸道神經內分泌物質對神經纖維延長和腸道痛覺異常的影響 | zh_TW |
| dc.title | Effects of enteric neuroendocrines on nerve fiber elongation and intestinal hypernociception | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孫錦虹(Chin-Hung Sun),忻凌偉(Ling-Wei Hsin) | |
| dc.subject.keyword | 腸躁症,精神壓力,梨形蟲,內臟高敏感性,神經纖維生長, | zh_TW |
| dc.subject.keyword | irritable bowel syndrome,psychological stress,Giardia lamblia,visceral hypersensitivity,neurite outgrowth, | en |
| dc.relation.page | 92 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位： | 生理學科所 | |
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