臺灣博碩士論文加值系統

膽固醇結石是現在社會上常見的文明病之一，而膽固醇(Ch)的結晶為膽固醇結石形成過程中之關鍵因子，因此，過飽和膽汁中Ch結晶的出現會有助於膽固醇結石形成，為了預防及治療膽固醇結石的發生，探討Ch結晶形成的原因則是非常重要的事情。在過去，膽固醇的過飽和被認為是結晶形成的唯一驅動力，但後來發現膽汁中過飽和膽固醇只是形成結晶的條件之一，而從熱力學的角度所觀察的膽固醇活動力值(thermodynamic activity of cholesterol, Ch AT)才是結晶的真正驅動力，而微脂粒(vesicles)的存在僅提供結晶所需的位置。本實驗針對親脂性膽鹽taurochenodeoxycholate (TCDC)-lecithin(L)及taurocholate (TC)-lecithin(L)系統，於不同的膽固醇飽和指數(cholesterol saturation index, CSI=2.0、2.3、2.5)和不同的Ch AT條件下，配製八種不同濃度比例 [TCDC/L=111.9-22 mM (TCDC/L=5.1)、TCDC/L=72.9-21.2 mM (TCDC/L=3.4)、TC/L=111.9-22 mM (TC/L=5.1)、TC/L=72.9-21.2 mM (TC/L=3.4)]之過飽和TCDC-L-Ch及TC-L-Ch模擬膽汁並對Ch結晶進行定量分析，結果發現不論TCDC-L-Ch或是TC-L-Ch，兩者濃度比例中BS/L=5.1溶液有較早的結晶出現、有較快的結晶速度、有較多的結晶生成，BS/L=3.4溶液居次，表示膽固醇活動力值越高者，越能促進結晶的形成及析出；反觀在不同CSI的變化下雖然CSI較高的有較多膽固醇析出，但是所觀測到膽固醇結晶析出的時間及速率並沒有太明顯的差別，所以造成的影響較小。此外，利用粒徑分析儀測定模擬膽汁於微脂粒(300~400 Å)出現時之濃度指數(concentration index)，結果發現微脂粒只是提供膽固醇結晶所需的位置，並不會對膽固醇結晶造成太大的影響。

Cholelithiasis is a kind of common diseases now. Previous studies have shown that cholesterol(Ch) nucleation is a key for Ch gallstone formation. Thus, appearance of Ch nucleation in supersaturated biles is an indication to Ch gallstone formation. To prevent the occurrence of Ch gallstones, investigation of Ch nucleation in supersaturated biles is very important. In the past, supersaturation of Ch in bile was mistakenly believed to be the only driving force for Ch gallstones. Later studies indicated that supersaturation of Ch in bile was a necessity but not the only requirement for Ch gallstone formation, whereas thermodynamic activity of cholesterol (Ch AT) was reported to be the true driving force for Ch nucleation. In addition, vesicles only provided nucleation sites. We chose two different bile salts, taurochenodeoxycholate (TCDC) and taurcholate (TC), and investigated the Ch crystallization quantitatively in supersaturated TCDC- Lecithin(L)-Ch and TC- Lecithin(L)-Ch model biles. Eight model biles [TCDC/L=111.9-22mM (TCDC/L=5.1), TCDC/L=72.9-21.2 mM (TCDC/L=3.4), TC/L=111.9-22mM (TC/L=5.1), TC/L=72.9-21.2mM (TC/L=3.4)] with different values of Ch saturation index (CSI=2.0, 2.3, 2.5) and Ch AT were prepared. Results indicate that regardless of the TCDC-L-Ch or the TC-L-Ch system, saturated solutions with BS/L=5.1 exhibit earlier appearance, faster crystallization rate, and larger amount of Ch crystallizations, compared to the saturated solutions with BS/L=3.4. It shows that the higher Ch AT is, the more favorably Ch crystallizes. Although the saturated solutions with higher CSI cause more Ch crystallization, difference in the nucleation process is not obvious. The result indicates that CSI does not influence Ch crystallization directly when the Ch AT values are nearly the same. Furthermore, concentrations of vesicles (300 ~ 400 Å) in different kinds of model biles can be determined by a particle size analyzer. Results together with Ch AT values in model biles show that the vesicles are only provided for the site of Ch crystallization.

中文摘要 ………………………………………………………… i
英文摘要 ………………………………………………………… iii
目錄 ……………………………………………………………… v
圖目錄 …………………………………………………………… vii
表目錄 …………………………………………………………… x


第一章 緒論
1.1前言 ………………………………………………………… 1

第二章 文獻回顧
2.1 膽汁………………………………………………………… 8
2.1.1 膽汁的特性 ……………………………………………… 8
2.1.2 膽固醇 …………………………………………………… 10
2.1.3 磷脂質 …………………………………………………… 11
2.1.4 膽鹽 ……………………………………………………… 12
2.2 膽汁中微胞之形成 ………………………………………… 17
2.2.1 簡單微胞 ………………………………………………… 18
2.2.2 BS-L複合微胞 ………………………………………… 19
2.3 微脂粒 ……………………………………………………… 21
2.4膽固醇活動力值 …………………………………………… 24

第三章 問題陳述
3.1 過飽和TCDC-L-Ch及TC-L-Ch系統之膽固醇結晶析出實驗 30
3.2過飽和TCDC-L-Ch及TC-L-Ch系統之粒徑分析實驗 ……… 31

第四章 過飽和TCDC-L-Ch及TC-L-Ch系統之膽固醇結晶析出實驗
4.1 簡介 ………………………………………………………… 32
4.2 材料與方法 ………………………………………………… 33
4.2.1 模擬膽汁配製及取樣 …………………………………… 33
4.2.2 膽固醇含量分析 ………………………………………… 36
4.3 結果與討論 ………………………………………………… 39
4.3.1 檢量線 …………………………………………………… 39
4.3.2 膽固醇含量分析 ………………………………………… 41

第五章 過飽和TCDC-L-Ch及TC-L-Ch系統之粒徑分析實驗
5.1 簡介………………………………………………………… 54
5.2 材料與方法 ………………………………………………… 62
5.2.1標準品量測 ……………………………………………… 62
5.2.2樣品量測 ………………………………………………… 63
5.3 結果與討論 ………………………………………………… 65
5.3.1 標準品之粒徑分析探討 ………………………………… 65
5.3.2 過飽和TC-L-Ch模擬膽汁之粒徑分析探討 …………… 67


第六章 結論
6.1 總論 ………………………………………………………… 79
6.2未來展望 …………………………………………………… 80

參考文獻 ………………………………………………………… 81


圖目錄
圖1-1 肝膽在消化系統的位置 ……………………………… 6
圖1-2 膽固醇結石的生成原因 ……………………………… 7
圖2-1 膽固醇分子結構 ……………………………………… 11
圖2-2 Lecithin分子結構 …………………………………… 12
圖2-3 膽鹽 (TC、TUDC、TCDC、THDC) 的化學結構 ……… 13
圖2-4 人體膽汁中，一級、二級和三級膽鹽合成代謝之化學結構
及位置 ………………………………………………… 14
圖2-5 膽鹽的腸肝循環 ……………………………………… 16
圖2-6 膽鹽簡單微胞聚集過程 ……………………………… 20
圖2-7 複合微胞類桿狀結構之主要兩種模型A. stacked-disk
model ,B. radial-shell model …………………… 20
圖2-8 微脂粒結構圖 ………………………………………… 22
圖2-9 TC-L-Ch模擬膽汁系統之Ch AT對CSI關係圖 ……… 28
圖3-1 膽固醇結石形成之三種成因 ………………………… 29
圖4-1 TCDC/L=5.1、3.4檢量線關係比較圖 ……………… 40
圖4-2 TC/L=5.1、3.4檢量線關係比較圖 ………………… 40
圖4-3 靜置37℃下，TCDC/L=5.1、3.4系統，膽固醇隨時間結晶析
出之關係曲線圖 ……………………………………… 43
圖4-4 靜置37℃下，TC/L=5.1、3.4系統，膽固醇隨時間結晶析
出之關係曲線圖 ……………………………………… 43
圖4-5 靜置37℃下，TCDC/L=5.1 CSI=2.0與CSI=2.5，膽固醇隨時
間結晶析出之關係曲線圖 …………………………… 44
圖4-6 靜置37℃下，TCDC/L=3.4 CSI=2.0與CSI=2.3，膽固醇隨時
間結晶析出之關係曲線圖 …………………………… 44
圖4-7 靜置37℃下，TC/L=5.1 CSI=2.0與CSI=2.5，膽固醇隨時
間結晶析出之關係曲線圖 …………………………… 45
圖4-8 靜置37℃下，TC/L=3.4 CSI=2.0與CSI=2.3，膽固醇隨時
間結晶析出之關係曲線圖 …………………………… 45
圖5-1 Microtrac UPA 150 粒徑分析儀 …………………… 55
圖5-2 樣品裝載示意圖 ……………………………………… 57
圖5-3 粒徑分佈圖 …………………………………………… 58
圖5-4 摘要訊息示意圖 ……………………………………… 58
圖5-5 量測結果訊息示意 …………………………………… 58
圖5-6 標準品30倍稀釋下concentration index值vs.濃度關係
圖 ……………………………………………………… 66
圖5-7 標準品濃度c之粒徑分析結果圖 ……………………… 69
圖5-8 標準品濃度c/2之粒徑分析結果圖 …………………… 70
圖5-9 標準品濃度c/3之粒徑分析結果圖 …………………… 71
圖5-10 標準品濃度c/4之粒徑分析結果圖 ………………… 72
圖5-11 標準品濃度c/5之粒徑分析結果圖 ………………… 73
圖5-12 標準品濃度c/6之粒徑分析結果圖 ………………… 74
圖5-13 標準品濃度c/8之粒徑分析結果圖 ………………… 75
圖5-14 標準品濃度c/10之粒徑分析結果圖 ………………… 76
圖5-15 TC/L=3.4 CSI=2.0溶液之粒徑分析結果圖 ………… 77
圖5-16 TC/L=3.4 CSI=2.3溶液之粒徑分析結果圖 ………… 78




表目錄
表2-1 人體膽汁的成份 ……………………………………… 9
表2-2 人體內膽囊與膽道中的膽汁比較 …………………… 10
表4-1 TCDC/L=5.1、3.4及TC/L=5.1、3.4之檢量線於不同膽固醇
濃度之吸光值 ………………………………………… 39
表4-2 TCDC/L=5.1 CSI=2.0溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 46
表4-3 TCDC/L=5.1 CSI=2.5溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 47
表4-4 TCDC/L=3.4 CSI=2.0溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 48
表4-5 TCDC/L=3.4 CSI=2.3溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 49
表4-6 TC/L=5.1 CSI=2.0溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 50
表4-7 TC/L=5.1 CSI=2.5溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 51


表4-8 TC/L=3.4 CSI=2.0溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 52
表4-9 TC/L=3.4 CSI=2.3溶液，靜置恆溫37℃下吸光值數據
處理表 ………………………………………………… 53
表5-1 量測時間參考表 ……………………………………… 57
表5-2 標準品粒徑分析下之數據列表 ……………………… 66
表5-3 TC/L=3.4 CSI=2.0溶液粒徑分析下之數據列表 …… 68
表5-4 TC/L=3.4 CSI=2.3溶液粒徑分析下之數據列表 …… 68

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