2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38076Cardiovascular disease is one of the most common causes of death in Taiwan. Due to its etiology is closely associated with the diet, change the dietary pattern by reducing risk factor and increasing protective factor intake is thought to be important in the prevention of this chronic disease. Cardiovascular disease is a multi-factors chronic disease. Among those factors, oxidatively modified low-density lipoprotein (oxidized LDL, oxLDL) plays a critical role in the initiation and progression of atherosclerosis. Indeed, oxLDL stimulates endothelial cells to produce a number of pro-inflammatory molecules including adhesion molecules and growth factors, which results in the recruitment of monocytes into the vessel wall and transforms to the foam cells. Expression of cell surface adhesion molecules is one of the key steps in the early events of atherosclerosis. Garlic has been used as a traditional medicine for prevention and treatment of cardiovascular diseases. However, the molecular action of garlic is not fully understood yet. Data suggest that garlic and its organosulfur compounds (OSCs) in the prevention of cardiovascular disease is possibly related to their biological activity in the lowering blood cholesterol, inhibiting platelet aggregation, suppressing oxidative stress, ameliorating chronic inflammation, and inducing apoptosis. Diallyl sulfide (DAS), diallyl disulfide (DADS), and DATS are three major lipid-soluble OSCs of garlic oil. Our preliminary data indicated that 100 microM DATS attenuated oxLDL induced VCAM-1 and E-selectin expression in Human umbilical vein endothelial cells. The potency of DAS was much lower than DATS. Protein kinase B (PKB), one of the serine-threonine kinase, is known to be an important signal mediator in regulating adehesion molecule expression in the endothelial cells. Additionally, PKB is also known to participate in the cell proliferation and survival. Base on the important role of adehesion molecules during atherosclerosis, it is interesting to examine whether DAS, DADS, and DATS are capable of counteracting oxLDL induced ICAM-1, VCAM-1, and E-selectin expression, and to determine what the role of PKB/Akt activation in this process.慢性心血管疾病在很多開發國家均是其國民名列前茅的死因，台灣也不例外，衛生署公佈九十二年國人十大死因排名中，腦血管疾病、心臟疾病、高血壓性心臟病已分居第二、三、十位，顯見心血管疾病已成為現代人的「隱形殺手」。不少心血管疾病的發生與飲食有密切關係，所以排除或減少飲食中危險因子接觸機會或增加保護因子的攝食，就成為預防這些疾病的重要課題。發炎(inflammation)是身體防禦微生物入侵時的正常反應，然而過度或不當的發炎也是不少慢性疾病發生的原因，其中粥狀動脈硬化就被視為慢性發炎相關疾病的一種。氧化修飾(oxidation modification)的低密度脂蛋白(LDL)在粥狀動脈硬化的起始及產生扮演一個重要的角色，對血管內皮細胞而言，氧化態低密度脂蛋白 (oxidized LDL, ox-LDL)已知會損害內皮細胞，產生發炎反應，並誘使細胞激素的分泌、激發黏附分子不正常的表現、淋巴細胞與單核細胞侵入血管壁、泡沫細胞生成、血管壁肌肉細胞增生等。黏附分子是發炎反應標記物質，在粥狀動脈硬化過程中具有舉足輕重的角色。粥狀動脈硬化形成的早期過程中，黏附分子是使白血球黏著到血管內皮細胞並進入血管壁內的關鍵因子，在一些臨床研究中顯示，粥狀動脈硬化患者的血漿中其黏附分子(P-selectin和ICAM-1)的表現是增加的。隨著時代的變遷，越來越多的人已了解到食物除了提供營養素外，同時存在於食物中所謂植物性化合物(phytochemicals)，也可能具有不容忽視的生理機能性，例如酚類化合物、大豆異黃酮、類黃酮、類胡蘿蔔素等，所表現出的免疫調節活性、抗氧化活性、抑制腫瘤生長活性、降血脂質活性等，便廣為受到重視。因此，將之納入均衡飲食概念中，也是預防保健的有效方法之一。近年來，大蒜在預防心血管疾病的相關研究，以探討後熟大蒜的水溶性萃出物及其主要的有機硫化合物S-allylcysteine (SAC)為主，實驗結果也顯示後熟大蒜與SAC無論在降血膽固醇、抑制血小板凝集、抗氧化作用或抑制iNOS表現上均有不錯的效果，顯示後熟大蒜在預防心血管疾病的應用性。至於脂溶性成分雖也有不少的研究，但以diallyl sulfide (DAS)及diallyl disulfide (DADS)最為常見，且研究主要以降血膽固醇、抗氧化、抑制腫瘤等方面為主，對於其抑制粥狀動脈硬化的精確機制尚未清楚。至於另一重要硫成分-diallyl trisulfide (DATS)，也是大蒜精油中主要的有機硫化合物之一(含量僅次於DADS)，則是尚未見諸報導。近來，本實驗室曾以DAS, DADS, DATS三種大蒜脂溶性成分預處理人類臍帶靜脈內皮細胞(Human umbilical vein endothelial cells, HUVECs)，探討ox-LDL誘發黏附分子表現之效應，初步結果指出：大蒜脂溶性成分中DADS及DATS具有抑制ox-LDL誘發黏附分子表現之效應。絲氨酸-酥氨酸激脢(serine-threonine kinase)中的Protein kinase B (PKB)是參與細胞增生 (proliferation)及存活 (survival)之重要訊息傳遞因子，而PKB路徑活性的維持與血管內皮細胞正常功能有密切關係，且ox-LDL會明顯抑制PKB活性。本計劃將以HUVECs為對象，在ox-LDL的處理下，分析黏附分子(ICAM-1, VCAM-1, E-selectin)蛋白質與mRNA表現、PKB磷酸化、單核球的黏著表現，探討大蒜及其組成分抑制ox-LDL誘發黏附分子表現，及其抑制效應與PKB路徑之相關性。血管內皮細胞在維持血管正常運作是不可或缺的，內皮細胞如果受傷，則易導致各種心血管方面的疾病。細胞黏附分子（cell adhesion molecules）也是討論內皮細胞與粥狀動脈硬化相關性時的焦點之一，所以可廣泛的運用此內皮細胞模式探討保健食品對預防心血管疾病的功能性評估。大蒜萃取物有機硫成分粥狀動脈硬化氧化態低密度脂蛋白黏附分子garlic extractsorganosulfur compoundsatherosclerosisoxidized LDLadehesion moleculesProject