探討芝麻素對腫瘤壞死因子刺激人類主動脈內皮細胞表現細胞黏附分子的影響及相關機轉

The effects of sesame lignans on adhesion molecules expression in tumor necrosis factor treated human aorta endothelial cells and the related mechanisms

高雅詩(Ya-shi Kao)

指導教授 ： 吳文惠 ； 陳玉怜

國立臺灣師範大學/教育學院/人類發展與家庭學系/碩士(2006年)

摘要

在動脈硬化發生早期，血流中白血球的黏附和遷移入血管壁為主要因素，而內皮細胞所分泌的細胞黏附分子，則在動脈硬化過程中扮演了重要的角色。抗氧化物可以抑制細胞黏附分子的表現，並且可以降低動脈硬化發生的機會。本實驗中，主要探討以芝麻木質素sesamol與sesamin處理人類主動脈內皮細胞（HAECs）表現細胞黏附分子的影響及相關機制。以sesamol (100 μM)或sesamin (100 μM)預先處理HAEC 24小時，可以顯著的抑制U937細胞黏附於內皮細胞。以西方墨點法得知處理sesamol或是sesamin可以抑制TNF-α刺激細胞黏附分子ICAM-1的表現。觀察MAPK主要途徑ERK1/2、JNK及p38的磷酸化，發現sesamin可以抑制ERK1/2與p38的磷酸化。此外，NF-κB p65免疫染色及凝膠遲滯分析結果顯示，sesamol及sesamin均可降低NF-κB的活性。實驗結果證實，sesamin可以藉由抑制ERK1/2 與 P38的磷酸化及降低NF-κB活性，減少細胞受TNF-α刺激所引發的ICAM-1表現。由上述結果得知：芝麻木質素可藉由拮抗內皮細胞失調及發炎反應，達到保護心血管的功能。

關鍵字

動脈硬化 ； 發炎反應 ； 黏附分子 ； 芝麻木質素

並列摘要

The adhesion and migration of circulating leukocytes into the vessel wall is an early event in atherogenesis and the expression of cell adhesion molecules by the arterial endothelium plays a major role during atherogenesis. Antioxidants have been proposed to inhibit the expression of adhesion molecules and thereby attenuate the processes leading to atherosclerosis. In this study, the effects of antioxidant of sesame lignans, sesamol and sesamin, on the expression of adhesion molecules and the associated related mechanisms in tumor necrosis factor-α (TNF-α) treated human aortic endothelial cells (HAECs) were investigated. HAECs pretreated with sesamol (100μM) or sesamin (100 μM) for 24 h significantly suppressed cellular binding between the human monocytic leukemic cell line-U937 and TNF-α treated HAECs. Western blotting analysis showed that the treatment of sesamol (100μM) or sesamin (100 μM) for 24h significantly attenuated intercellular cell adhesion molecule-1 (ICAM-1) expression in HAECs under TNF-α stimulation. Phosphorylation studies on ERK1/2, JNK, and p38, three major subgroups of mitogen activator protein kinases, demonstrated that sesamin suppressed ERK1/2 and p38 phosphorylation. In addition, sesamol and sesamin significantly decreased the expression of NF-κB p65 and the activity of NF-κB by immunostaining and gel-mobility shift assay, respectively. These results provide the evidence that sesamin attenuated ICAM-1 expression caused by TNF-α stimulation and this inhibitory effect is mediated via downregulation of ERK1/2 and P38 phosphorylation and inactivation of NF-κB. These observation support the feasibility of sesame lignans administration is as a means of protection against endothelial dysfunction and inflammation.

並列關鍵字

atherosclerosis ； inflammatory ； adhesion molecule ； sesame lignans

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