| 摘要: | 內皮細胞表現黏附因子，以及單核球黏附於內皮細胞上，在動脈粥狀硬化過程中扮演一個重要的角色。綠原酸（chlorogenic acid）為ㄧ種酚酸物質，主要存在於咖啡、蘋果、梨、莓類、桃仁、朝鮮薊和茄子中，在過去的體外實驗中指出綠原酸具有抗氧化活性。而在此次實驗中，主要探討綠原酸對於IL-1β所誘導人類臍靜脈內皮細胞ROS及黏附因子表現之影響，並且和probucol比較其效果。結果顯示，綠原酸抑制LDL氧化之IC50為3.1 ±0.4 μM，而Probucol之IC50值為5.5 ±0.7 μM；綠原酸清除DPPH自由基之IC50值約為36.3 ±2.7 μM，而Probucol之IC50值約為41.8 ±3.1 μM。藉由同步定量聚合脢鏈反應發現，綠原酸可降低IL-1β所誘導之VCAM-1, ICAM-1及E-selectin之mRNA表現，且抑制效果隨劑量增加而增強。綠原酸也能減少IL-1β所誘導之細胞中ROS。同時發現綠原酸可減低或阻斷IL-1β所誘導之核轉錄因子NF-κB P50, P65, P52, Rel-B, C-Rel的活化，亦表示綠原酸降低黏附因子表現是屬於轉錄層次的調控。此外綠原酸可顯著降低IL-1β所誘導之人類單核球細胞（U-937）之黏附，並且發現抑制效果隨劑量增加而增強。此研究的結果證實綠原酸在體外實驗中具有抑制早期動脈粥狀硬化發展之作用。
Expression of cell adhesion molecules （CAM）by the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. Chlorogenic acid（CA）is a phenolic compound present in coffee, apple, pears, berries, almond, artichoke and aubergines. Previous study indicated that CA possess antioxidant activity in vitro. In this study, the effect of CA on the formation of intracellular reaction oxygen species（ROS）and expression of CAM in IL-1β induced human umbilical vein endothelial cells（HUVEC）were investigated, and compared with the control probucol. Our data showed that the inhibition of LDL oxidation（IC50）of CA and probucol were 3.1 ±0.4 μM and 5.5 ±0.7 μM, respectively. The Scavenging ability of DPPH radical（IC50）of CA and probucol were 36.3 ±2.7 μM and 41.8 ± 3.1 μM, respectively. CA dose-dependently suppressed IL-1β-induced mRNA expression on vascular cell adhesion molecule-1（VCAM-1）, intercellular cell adhesion molecule-1（ICAM-1）and endothelial cell selectin（E-selectin）by real-time PCR analysis. CA also suppressed IL-1β-induced the production of ROS. We observed that CA attenuated or blocked nuclear translocation of nuclear factor-κB（NF-κB）P50, P65, P52, Rel-B and C-Rel stimulated by IL-1β, which in turn attenuated CAM expression at the transcription level. Furthermore, CA significantly reduced the adhesion of humans monocyte cell line, U937, to HUVEC treated IL-1β in a dose-response manner. These results demonstrate that CA has inhibitory effect on proanthersclerotic mechanism in vitro. |
