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系統識別號 U0007-2807200714042800
論文名稱(中文) 大蒜有機硫化合物diallyl sulfide與diallyl disulfide對血管新生作用及其相關因子之影響
論文名稱(英文) Effects of diallyl sulfide and diallyl disulfide on angiogenesis and angiogenesis-related factors
校院名稱 臺北醫學大學
系所名稱(中) 保健營養學研究所
系所名稱(英) Graduate Institute of Nutrition and Health
學年度 95
學期 2
出版年 96
研究生(中文) 周歆倩
研究生(英文) Sin-Chien Chou
學號 M507094012
學位類別 碩士
語文別 中文
口試日期 2007-07-06
論文頁數 119頁
口試委員 指導教授-陳玉華
委員-郭明良
委員-蕭哲志
中文關鍵字 大蒜有機硫化合物  血管新生  癌症  傷口癒合 
英文關鍵字 garlic organosulfur compounds  angiogenesis  wound healing  carcinogenesis 
學科別分類
中文摘要 本研究為利用細胞及動物模式探討大蒜有機硫化合物對血管新生作用及其相關因子之影響。細胞實驗方面,分別在有無10 ng/ml VEGF投予下,給予血管內皮EA hy 926細胞DAS (diallyl sulfide) 及DADS (diallyl disulfide) 後,分析有機硫化合物對細胞生長及血管新生相關因子之影響。結果顯示,大蒜萃取物DAS (2.5~7.5 μM) 及DADS (0.05~0.5 μM) 可抑制EA hy 926細胞之生長與增生,但可促進血管新生過程最後階段-類血管 (tube formation) 之生成,且此影響與促血管新生因子VEGF、IL-8及活化型MMP-2表現增加相關。在VEGF誘導血管新生下,DAS、DADS及二者合併使用皆可抑制因VEGF誘導之EA hy 926細胞增生及類血管生成,其影響與增加IL-8及降低活化型MMP-2表現相關。於動物實驗方面,以皮下注射含有無1 μg/ml bFGF (basic fibroblast growth factor) 之matrigel,以誘導C57BL/6小鼠病理性血管新生作用後,結果顯示,連續10天腹腔注射DAS (12.5 mg/kg)、DADS (50 mg/kg) 及合併使用組別,matrigel中之血紅素含量有低於bFGF組之傾向,但無顯著差異。總而言之,大蒜可促進細胞生理性血管新生,且抑制VEGF誘導之細胞血管新生作用,其作用與調節血管新生相關因子VEGF、IL-8及MMP-2表現相關,但動物實驗結果有待進一步確認之。

關鍵字: 大蒜有機硫化合物、血管新生、癌症、傷口癒合
英文摘要 This study was aimed at studying the effects of diallyl sulfide (DAS) and diallyl disulfide (DADS), organosulfur compounds derived form garlic (Allium sativum L.), on the process of angiogenesis. In cultured cells, DAS (2.5~7.5 μM) and DADS (0.05~0.5 μM) enhanced tube formation of EA hy 926 cells, and which was associated with up-regulated expression of pro-angiogenic factors, including VEGF, IL-8 and activated MMP-2 (p<0.05). On the other hand, DAS, DADS, as well as combination of DAS and DADS (0.5+0.005 μM, 1+0.01 μM) inhibited VEGF-stimulated tube formation and activated MMP-2 expression, but increased IL-8 production in EA hy 926 cells (p<0.05). In animals, pathological angiogenesis were induced by subcutaneously injection of 1 μg/ml bFGF-contained matrigel followed by daily ip. injection of DAS (12.5 mg/kg), DADS (50 mg/kg) and DAS+DADS for 10 days. The results showed that DAS, DADS and DAS+DADS mixture did not significantly suppress bFGF-induced hemoglobin contents in matrigels. In summary, DAS and DADS enhanced tube formation under a basal state, but suppressed tube formation in VEGF-stimulated pathological condition, indicating the potential roles of garlic in promoting wound healing as well as in inhibiting carcinogenesis.

key words: garlic organosulfur compounds, angiogenesis, wound healing, carcinogenesis
論文目次 中文摘要 I
Abstract III
致謝 V
圖目次 VIII
表目次 X
第一章 緒論 1
第二章 文獻回顧 3
第一節 癌症與血管新生作用 3
第二節 血管新生作用與傷口癒合 6
第三節 血管新生相關因子 7
第四節 大蒜及其萃取物 15
第五節 大蒜萃取物與癌症及血管新生之相關性 19
第三章 材料與方法 22
第一節 試劑 22
第二節 儀器 26
第三節 細胞培養 27
第四節 動物飼養 28
第五節 實驗流程 29
第六節 細胞毒性之分析 34
第七節 細胞增生之分析 35
第八節 類血管生成 (tube formation) 之分析 36
第九節 血管內皮細胞生長因子 (VEGF) 之分析 37
第十節 細胞激素IL-8之分析 38
第十一節 蛋白質定量之分析 39
第十二節 Gelatin zymography之分析 40
第十三節 matrigel之血紅素分析 42
第十四節 全血之血紅素分析 43
第十五節 統計分析 44
第四章 結果 45
第一節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞生長之影響 45
第二節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞毒性之影響 48
第三節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞類血管生成之影響 50
第四節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞VEGF表現之影響 53
第五節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞IL-8表現之影響 55
第六節 大蒜有機硫化合物DAS、DADS對EA hy 926細胞MMP表現之影響 57
第七節 大蒜有機硫化合物DAS、DADS及DAS+DADS對VEGF誘導之EA hy 926細胞生長之影響 60
第八節 大蒜有機硫化合物DAS、DADS及DAS+DADS對VEGF誘導之EA hy 926細胞毒性之影響 64
第九節 大蒜有機硫化合物DAS、DADS及 DAS+DADS對VEGF誘導之EA hy 926細胞類血管生成之影響 67
第十節 大蒜有機硫化合物DAS、DADS及DAS+DADS對VEGF誘導之EA hy 926細胞IL-8表現之影響 71
第十一節 大蒜有機硫化合物DAS、DADS及DAS+DADS對VEGF誘導之EA hy 926細胞MMP表現之影響 74
第十二節 大蒜有機硫化合物DAS、DADS及DAS+DADS對C57BL/6小鼠體重及相對組織重量之影響 78
第十三節 大蒜有機硫化合物DAS、DADS及DAS+DADS對C57BL/6小鼠內以bFGF誘導之matrigel中血管新生影響 80
第十四節 大蒜有機硫化合物DAS、DADS及DAS+DADS對C57BL/6小鼠之血液血紅素之影響 83
第五章 討論 85
第一節 DAS及DADS對細胞生理性血管新生作用之影響 85
第二節 DAS及DADS對細胞病理性血管新生作用之影響 88
第三節 DAS及DADS對動物病理性血管新生作用之影響 91
第六章 結論 94
第七章 參考文獻 95


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