穿心蓮內酯對腫瘤壞死因子誘發人類臍靜脈內皮細胞黏著因子 ICAM-1 表現之探討

Effect of andrographolide on tumor necrosis factor-alpha-induced expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells

朱倖槿(Hsing-Chin Chu)

指導教授 ： 劉凱莉 ； 陳暉雯

中山醫學大學/健康管理學院/營養學研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00057

摘要

動脈粥狀硬化是長期發炎所累積而成的一種病症，其形成的初期過程包含氧化型低密度脂蛋白過度累積並活化血管內皮細胞以及誘發內皮細胞表現黏著分子並吸引血液循環中的白血球黏附到血管內皮細胞。研究指出氧化型低密度脂蛋白會刺激巨噬細胞分泌發炎性細胞激素腫瘤壞死因子 (tumor necrosis factor-α)，因此氧化型低密度脂蛋白被認為是一種促發炎刺激。穿心蓮內酯是一種 diterpene lactone，主要分佈於穿心蓮葉子中，目前證實穿心蓮內酯具有抗癌、保護肝臟與抗發炎等活性。本研究觀察穿心蓮內酯對腫瘤壞死因子誘發單核球黏附至人類臍靜脈內皮細胞的影響，發現穿心蓮內酯可有效抑制 HL-60 細胞株黏附至人類臍靜脈內皮細胞，也可抑制黏著分子 ICAM-1 總蛋白質與細胞表面的表現，以及抑制 ICAM-1 報導基因活性。穿心蓮內酯也可抑制腫瘤壞死因子誘發的 Akt 磷酸化，而且細胞預處理 PI3K 抑制劑 LY294002 也可顯著降低腫瘤壞死因子誘發的 ICAM-1 報導基因活性。此外，穿心蓮內酯也會減少 p65 進入細胞核內以及 NF-κB 與 DNA 的結合。這些結果顯示在人類臍靜脈內皮細胞中，穿心蓮內酯可藉由PI3K/Akt 或 NF-κB負向調控 ICAM-1 表現而具有抗發炎作用，本研究證實穿心蓮內酯在預防發炎反應形成過程扮演重要角色。

關鍵字

穿心蓮內酯 ； TNF-α ； NF-κB ； ICAM-1 ； 人類臍靜脈內皮細胞 ； PI3K/Akt

並列摘要

Atherosclerosis is an inflammatory disease in which the early stages of atherosclerosis are initiated by accumulation of oxLDL and activation of endothelial cells with subsequent expression of adhesion molecules and increased recruitment of leukocytes to the vascular endothelium. It is reported that stimulation of macrophages with oxLDL leads to enhanced TNF-α secretion. TNF-α is an inflammatory cytokine, and this implicates that oxLDL is an inflammatory stimulus. Andrographolide is a diterpene lactone isolated from the leaves of the Andrographis paniculata, which has been shown to possess anticancer, hepato-protective, and antiinflammatory activities. This study examined the effects of andrographolide on TNF-α-induced monocyte/human endothelial cell interaction. Andrographolide inhibited the adhesion of HL-60 cells to TNF-α-induced human umbilical vein endothelial cells (HUVECs) and suppressed total protein, cell surface expression and the promoter activity of the intracellular adhesion molecules-1 (ICAM-1). Andrographolide also abolished TNF-α-induced phosphorylation of Akt (p-Akt) in a time-dependent manner, and the ICAM-1 promoter activity decreased when cells pretreated with PI3K inhibitor LY294002. Moreover, andrographolide blocked nuclear translocation and DNA binding activity of NF-κB. In summary, these results demonstrated that andrographolide exhibits an anti-inflammatory property by down-regulating the pathway that affects the expression of ICAM-1 and the action of andrographolide may be closely related to the inhibition of PI3K/Akt and NF-κB activation in HUVEC. This indicates that andrographolide may play an important role in the prevention of inflammatory responses such as the atherosclerosis process.

並列關鍵字

andrographolide ； tumor necrosis factor-α (TNF-α) ； nuclear factor-kappa B (NF-κB) ； intercellular adhesion molecule (ICAM-1) ； human umbilical vein

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