臺灣博碩士論文加值系統

甘氨醯-組氨醯-賴氨酸（glycyl-histidyl-lysine，GHK）是人體中的一種三肽，已有文獻證明它具有多種生物活性。本研究將GHK的衍生物之雙親性分子棕櫚醯甘氨醯 - 組氨醯 - 賴氨酸（palmitoyl glycyl-histidyl-lysine，Pal-GHK）與氫化大豆磷脂醯膽鹼（hydrogenated soy phosphatidylcholine，HSPC）和雙十六烷基磷酸酯（dihexadecyl phosphate，DHP）混合以形成脂質雙層（lipid bilayer）作為細胞膜的模型，並以多重技術評估Pal-GHK如何對HSPC和DHP模型膜的物理化學特性產生影響，其中包含：動態光散射、透射電子顯微鏡、熱差示掃描量熱法、螢光偏極化、衰減全反射傅立葉變換紅外光譜和Langmuir-Blodgett單分子層。在HSPC系統，當將Pal-GHK以莫耳分率（XPal-GHK = 0.1至0.3）加入HSPC分散液中時，主轉變溫度降低，螢光偏極化中，純HSPC分散液的行為進行比較，當XPal-GHK為0.1和0.3時，膜內流動性也增加，而在XPal-GHK接近0.4~0.7後，相較於XPal-GHK = 0.1~0.3而言，其膜內流動性低，而IR研究中，脂質膜的烷基鏈的堆疊密度變化也顯示出相似的變化。在DHP系統，膠體分散粒子的主轉變溫度和堆疊密度隨著Pal-GHK組成的增加都降低，而膜內流動性則隨組成的增加而增加。在單分子層研究中，Pal-GHK在高表面壓力下被迫脫離HSPC單分子層。然而與HSPC分子相比，帶正電的Pal-GHK有與帶負電的DHP分子產生更多相互作用的可能性。根據本研究之結果，Pal-GHK會使的HSPC和DHP模型膜的結構與分子堆疊與變得鬆散。此外根據上述實驗推測，在Pal-GHK莫耳分率為0.4至0.8的範圍內，HSPC的液胞雙層結構可能轉變為交叉式雙層。

Glycyl-histidyl-lysine (GHK) is a kind of tripeptide in the human body. It has been proven to exhibit several bioactivities. The amphiphilic molecules palmitoyl glycyl-histidyl-lysine (Pal-GHK) derived from GHK was mixed with hydrogenated soy phosphatidylcholine (HSPC) and dihexadecyl phosphate (DHP) to form lipid bilayer as models of the cell membrane. Multi˗techniques estimate the physicochemical characteristics and properties of HSPC and DHP model membrane affected by Pal-GHK. In the HSPC system, the main-transition temperature decreased when the molar fraction of Pal-GHK (XPal-GHK = 0.1 to 0.3) was added into the HSPC bilayer. By comparing with the behavior of pure HSPC dispersion, the membrane fluidity also increased when XPal-GHK is from 0.1 and 0.3. After XPal-GHK approached 0.4 ~ 0.7, their membrane fluidity was lower than those of XPal-GHK = 0.1 to 0.3. The packing density of lipid alkyl chain also shows a similar result in IR study. In the DHP system, the main-transition temperature, packing density of lipid alkyl chain decreased, and the membrane fluidity increased as increasing the amount of Pal-GHK. From the result of monolayer model, Pal-GHK was forced out of the HSPC monolayer at high surface pressure. However, Pal-GHK expresses more potential to interact with DHP molecules compared to HSPC. In summary, Pal-GHK loosens the packing of both HSPC and DHP model membrane. In addition, it can be suggested that HSPC vesicle structures may form the interdigitated bilayer with the Pal-GHK molar ratio at the range from 0.4 to 0.8.

摘要 i
Abstract ii
目錄 iii
表目錄 vi
圖目錄 vii
符號說明 xiii
第1章 緒論 1
1-1 前言 1
1-2 研究動機與目的 2
第2章 文獻回顧 3
2-1 藥妝品常用之抗皺胜肽 3
2-2 GHK與GHK-Cu 4
2-3 GHK之衍生物 5
2-4 脂質膜之模型 6
2-5 脂質雙層結構與分子自聚集和堆疊之間的關係 8
第3章 實驗材料與方法 12
3-1 實驗藥品 12
3-2 實驗方法與原理 13
3-2-1 膠體分散液製備 13
3-2-2 粒徑分析 13
3-2-3 界面電位分析 14
3-2-4 穿透式電子顯微鏡 15
3-2-5 微分式掃描熱卡計分析 16
3-2-6 螢光偏極化分析 17
3-2-7 傅立葉變換衰減全反射紅外光譜分析 18
3-2-8 Langmuir–Blodgett 單分子層技術 19
3-2-8-1 單分子層氣-液界面之表面張力量測 20
3-2-8-2 混合單分子層之表面壓與每分子佔據面積之等溫線量測 22
3-2-8-3 混合單分子層之螢光顯微影像分析 22
第4章 實驗結果與討論 29
4-1 HSPC/Pal-GHK混合分散液之物化特徵 29
4-1-1 HSPC/Pal-GHK混合分散液之粒徑、分散度與界面電位分析 29
4-1-2 HSPC/Pal-GHK混合分散液之粒子型態觀察 30
4-1-3 HSPC/Pal-GHK混合分散液之相變行為分析 31
4-1-4 HSPC/Pal-GHK混合分散液之膜內流動性分析 32
4-1-5 HSPC/Pal-GHK混合分散液之紅外光光譜分析 33
4-2 HSPC/Pal-GHK混合單分子層之行為與特性 37
4-2-1 HSPC/Pal-GHK混合單分子層之π–A等溫線分析 37
4-2-2 HSPC/Pal-GHK混合單分子層之界面型態觀察 38
4-3 DHP/Pal-GHK混合分散液之物化特徵 39
4-3-1 DHP/Pal-GHK 混合分散液之粒徑、分散度與界面電位分析 39
4-3-2 DHP/Pal-GHK混合分散液之粒子型態觀察 40
4-3-3 DHP/Pal-GHK混合分散液之相變行為分析 40
4-3-4 DHP/Pal-GHK混合分散液之膜內流動性分析 42
4-3-5 DHP/Pal-GHK混合分散液之紅外光光譜分析 43
4-4 DHP/Pal-GHK混合單分子層之行為 44
4-4-1 DHP/Pal-GHK混合單分子層之π–A等溫線分析 44
4-4-2 DHP/Pal-GHK混合單分子層之界面型態觀察 44
第5章 結論 93
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