中文摘要 粥狀動脈硬化是一個包含許多功能改變的疾病。氧化低密度脂蛋白（oxidative low density lipoprotein；ox-LDL）在此疾病中扮演一個極重要的角色；許多證據證明低密度脂蛋白及氧化低密度脂蛋白皆會刺激血管平滑肌細胞增生；氧化低密度脂蛋白同時也會引起血管平滑肌細胞的凋亡。Ellagic acid （EA）是一種存在於蔬果，如：藍莓、草莓和堅果類中的酚類化合物，可能具有抗氧化、抗癌細胞增生的功能。因此本論文研究ox-LDL刺激平滑肌細胞增生及凋亡與Ellagic acid 之間的相關性。 本研究使用3-4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-terazolium bromide（MTT）試驗及細胞計數的方式測得細胞之存活率，發現ox-LDL刺激引起的增生，可經由同步給予Ellagic acid 而有所改善。流式細胞儀測定細胞週期發現，經ox-LDL刺激平滑肌細胞之細胞週期S期增加，同步給予Ellagic acid 則可以明顯抑制增生。Ellagic acid 也可以抑制ox-LDL刺激所導致之平滑肌細胞蛋白質，ErK 1/2 、pErK 1/2、和PCNA 的表現增加。在凋亡方面，Ellagic acid 可以抑制細胞凋亡進行及細胞凋亡時形態的改變，亦可經抑制caspase的基因表現，進而改善凋亡之情形。這些結果提供食物中的抗氧化劑，可以預防粥狀動脈硬化疾病的發生。; 英文摘要 In the multifunctional pathogens of atherosclerosis, oxidatively modified low density lipoprotein plays a central role in atherogenesis. Previous studies demonstrated that both native LDL and ox-LDL could stimulate the proliferation of vascular smooth muscle cells. However ox-LDL has also been shown to induce apoptosis in vascular smooth muscle cells (VSMCs). Ellagic acid, an antioxidant, is a phenolic compound presenting in fruits (raspberries, blueberries, strawberries) and walnuts. In this study, we investigated whether VSMCs proliferation and apoptosis induced by ox-LDL would be affected by ellagic acid. Cell viability was tested by MTT test and cell count and study ox-LDL stimulated cell proliferation was inhibited by Ellagic acid. Ellagic acid suppressed the increased the percetage of cell cycle S phase induced by ox-LDL. The activitives of ErK 1/2 , pErK 1/2 and PCNA were also inhibited by ellagic acid. In apoptosis, ellagic acid also inhibited cell apoptosis and cell morphologic change. However ellagic acid suppressed expression of caspase genes could by ox-LDL. These results might significantly advance the understanding of the antioxidants implicated in the formation of atherosclerosis, and could eventually lead to the development of new dietary supplements for the prevention of atherosclerosis. Key word: Ellagic acid, Ox-LDL, Smooth muscle cell, Proliferation, Apoptosis.
