| Abstract: | 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。已知氧化修飾的低密度脂蛋白(ox-LDL)誘發血管內皮細胞黏附分子不正常的表現，在粥狀動脈硬化的起始及產生扮演一個重要的角色。在一些臨床研究中，粥狀動脈硬化患者血漿中的P-selectin和ICAM-1等黏附分子的濃度的確是較健康者高。近來，食物中所謂的植物性化合物(phytochemicals)可能具有的生理機能性已吸引越來越多的注意，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。大蒜在預防心血管疾病上雖已有不少相關研究，但在抑制ox-LDL誘發血管內皮細胞黏附分子表現的分子機轉上則仍有待釐清，本計劃將以人類臍帶靜脈內皮細胞(Human umbilical vein endothelial cells, HUVECs)為對象，探討在ox-LDL處理下，三種大蒜有機硫成分-DAS, DADS, and DATS對ox-LDL誘發血管內皮細胞黏附分子(ICAM-1, VCAM-1, E-selectin)表現表現之效應，並同時探討PKB路徑之角色。結果顯示：DADS and DATS可以有效抑制ox-LDL誘發E-selectin與VCAM-1蛋白及mRNA表現，同時細胞表面E-selectin與VCAM-1的表現也減少，至於ox-LDL誘發ICAM-1表現的現象僅輕微受到DADS and DATS的影響，相較DADS and DATS，DAS對黏附分子大量表現的保護效果則較低。ox-LDL抑制PKB磷酸化已知與其誘發黏附分子表現有關，DADS and DATS則對ox-LDL抑制PKB磷酸化有回復效果，而且DADS and DATS對E-selectin不正常大量表現的保護作用會因PKB磷酸化抑制劑-Wortnammin的處理而消失，然而DADS and DATS對ICAM-1的抑制作用並不因Wortnammin改變。這些結果指出：大蒜抗粥狀動脈硬化可能與其活性有機硫成分抑制血管內皮細胞黏附分子表現有關，其中PKB訊號途徑應在其保護E-selectin表現中扮演重要角色。
Cardiovascular disease is one of the most common causes of death in Taiwan recently. As the dysfunction of cerebral vascular, cardiac, and blood pressure is the highest risk factor causing death, the cardiovascular disorder is the ？§silent killer？？. Therefore, reducing the risk and increasing the protective factors from foods is an important way to prevent such diseases. Oxidized low-density lipoprotein (ox-LDL) plays a critical role in the initiation and progression of atherosclerosis. The induction of ox-LDL on the cell surface adhesion molecule expression is the key event in early events of atherosclerosis. In patients with atherosclerotic disease, serum levels of soluble P-selectin and ICAM-1 are elevated as compared with the healthy subjects. Recently, several phytochemicals including phenolic compounds, isoflavones, and carotenoids have been demonstrated to display diverse biological activities and, thus, are regarded as nutriceutical agents. Garlic has been used as a traditional medicine for prevention and treatment of cardiovascular diseases. However, the molecular mechanism of garlic active components on ox-LDL-induced adhesion molecule expression on vascular endothelial cells is not clearly elucidated yet. The present study was designed to examine the effect of DAS, DADS, and DATS on E-selectin, ICAM-1, and VCAM-1 expression in human umbilical vein endothelial cells (HUVECs) in the presence of ox-LDL. The role of PKB pathway was also investigated. Results showed DADS and DATS are effective on suppressing ox-LDL-induced E-selectin and VCAM-1 protein and mRNA levels and also their cells expression on cell surface. DAS, however, only a minor effect was noted. Compared to E-selectin and VCAM-1, ICAM-1 expression induced by ox-LDL was moderately inhibited by garlic organosulfur components. PKB phosphorylation was noted to be inhibited by ox-LDL. DADS and DATS reversed the inhibition of ox-LDL on PKB phosphorylation. Moreover, DADS and DATS suppressed ox-LDL-induced E-selectin expression was diminished by co-treating with Wortmannin, a PKB phosphorylation inhibitor. In contrast, the inhibition of VCAM-1 expression by garlic components was not changed by Wortmannin. Results suggest the antiatherosclerotic effect of garlic can be attributed to, at least in part, the effectiveness of DADS and DATS on the suppression of ox-LDL-induced adhesion molecule expression. Furthermore, PKB signal pathway is likely involved in the protection of DADS and DATS on E-selectin expression. |
