博碩士論文 111324026 詳細資訊




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姓名 林意萱(Yi-Shiuan Lin)  查詢紙本館藏   畢業系所 化學工程與材料工程學系
論文名稱 氯胺酮對仿生物膜與神經遞質釋放之影響
(Effects of Ketamine on Biomimetic Membranes and Neurotransmitter Release)
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檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2029-9-11以後開放)
摘要(中) 本研究重點關注氯胺酮(ketamine,俗稱K他命)對神經遞質(neurotransmitter)釋放和囊泡(vesicle)融合的影響,及其在憂鬱症治療中的應用。臨床研究顯示,氯胺酮可以快速且有效地緩解憂鬱症狀。目前的研究指出,氯胺酮的藥理治療可能與阻斷神經元(neuron)突觸間隙(synapse)中之谷氨酸(glutamic acid)的再吸收與神經元囊泡之釋放有關,但確切之作用機制仍有待釐清。因此,本研究將透過仿生脂質膜(biomimetic lipid membranes,作為神經元之細胞膜的模型系統)進行物理實驗,包括在膜融合實驗中氯胺酮是否影響融合程度釋放神經傳遞質,以及探討其原因是否為脂質膜的物理性質(脂雙層厚度和自發曲率)的改變,來進一步瞭解氯胺酮緩解憂鬱症狀的藥理機制。氯胺酮的存在對於脂雙層厚度及自發曲率並無太大變化,對於添加氯胺酮後的膜融合程度降低可能有其他原因。
摘要(英) This study focuses on the effects of ketamine on neurotransmitter release and vesicle fusion, and its application in the treatment of depression. Clinical studies show that ketamine can quickly and effectively relieve symptoms of depression. Current research points out that pharmacological treatment with ketamine may be related to blocking the reabsorption of glutamic acid and the release of neuronal vesicles in the synapse of neurons, but the exact mechanism of action Still to be clarified. Therefore, this study will conduct physical experiments through biomimetic lipid membranes (as a model system of neuronal cell membranes), including whether ketamine affects the extent of fusion and the release of neurotransmitters in membrane fusion experiments, and explore whether the reasons are. To further understand the pharmacological mechanism of ketamine in relieving depression symptoms through changes in the physical properties of lipid membranes (lipid bilayer thickness and spontaneous curvature). The presence of ketamine did not change the lipid bilayer thickness and spontaneous curvature much, and there may be other reasons for the reduced extent of membrane fusion after the addition of ketamine.
關鍵字(中) ★ 憂鬱症
★ 氯胺酮
★ 谷氨酸
★ 脂質膜
關鍵字(英) ★ Depression
★ ketamine
★ glutamate
★ lipid membrane
論文目次 摘要 I
Abstract II
誌謝 III
目錄 V
圖目錄 VIII
表目錄 XI
第一章 緒論 1
1-1簡介 1
1-2研究目的及動機 2
第二章 文獻回顧 3
2-1憂鬱症 3
2-1-1神經傳遞質(neurotransmitter) 5
2-1-2胞吐作用 8
2-2氯胺酮(ketamine) 10
2-3生物膜 13
2-4彈性性質(elastic property) 15
2-4-1彎曲模量(bending modulus) 15
2-4-2自發曲率(spontaneous curvature, C0) 16
第三章 實驗製備與儀器測量 19
3-1實驗材料 19
3-2實驗儀器 22
3-3樣品製備 23
3-3-1仿突觸囊泡膜 23
3-3-2仿神經細胞膜 25
3-3-3谷氨酸濃度標準曲線 26
3-3-4膜融合 28
3-3-5 HII phase 30
3-4儀器分析 32
3-4-1動態光散射(dynamic light scattering, DLS) 32
3-4-2螢光光譜儀(fluorescence spectrometer) 35
3-4-3 小角度X光散射(small angle x-ray scattering, SAXS) 37
3-5數據處理與分析 40
3-5-1 HII電子雲密度(HII electron density) 40
3-5-2量化自發曲率C0 44
3-5-3 脂質體(liposome)膜厚度 45
第四章 結果與討論 47
4-1仿神經細胞膜與仿突觸囊泡膜之DLS結果 47
4-2 氯胺酮對膜融合之影響 49
4-3 氯胺酮對脂質膜的結構和膜厚的影響與膜融合之關聯性 54
4-4自發曲率與膜融合之相關性 58
第五章 結論 65
參考資料 66
附錄 81
附錄一 膜融合-三獨立樣品重複實驗 81
附錄二 SAXS膜厚數據 83
附錄三 六角相擬合數據 87
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指導教授 陳儀帆(Yi-Fan Chen) 審核日期 2024-9-18
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