| 摘要: | 動脈粥樣化(atherosclerosis)是一種多因性的慢性發炎性心血管疾病，不正常的脂質代謝比如血中高低密度脂蛋白(LDL)或高氧化型LDL (ox-LDL)都在動脈粥樣化發展過程中扮演著關鍵角色。在早期病理發展過程中，ox-LDL會誘發血管內皮細胞表現大量黏著分子(adhesion molecules)，使得白血球在血管壁上黏附和滲透增加，ox-LDL也會促進血管平滑肌細胞增生及血栓發生的作用。異硫氰酸鹽(isothiocyanates)是富含於十字花科蔬菜中的有機硫化物，先前研究指出異硫氰酸鹽擁有多樣生理活性，包括保護心血管功能、活化phase II解毒酵素表現、抗腫瘤、促癌細胞凋亡等。本研究將以人類臍靜脈血管內皮細胞株(human umbilical vein endothelial cells, HUVEC)為實驗對象，在ox-LDL誘發模式下，探討benzyl isothiocyanate (BITC)、phenylethyl isothiocyanate (PEITC)及sulforaphane (SFN)三種異硫氰酸鹽對於E-selectin表現之影響和其作用機轉。結果顯示：(1)在40 M ox-LDL刺激下，5 M的BITC、PEITC及SFN預處理可抑制E-selectin蛋白質表現；(2)三種異硫氰酸鹽亦可減少HL60單核球與HUVEC的黏附；(3)三種異硫氰酸鹽也可誘發胞內第一型血基質氧化??(heme oxygenase-1)表現；(4) ox-LDL誘發胞內活性氧的生成會因BITC、PEITC及SFN預處理而受到抑制；(5) SFN預處理對ox-LDL誘發ERK磷酸化有抑制效果。結論：BITC、PEITC及SFN可能經由誘發HO-1表現減少氧化壓力，因此抑制ERK的活化，進而抑制血管內皮細胞E-selectin表現。
Atherosclerosis is regarded as a chronic inflammatory disease and its etiology is multifactorial. Abnormal lipid metabolism, such as increases in LDL concentrations in the circulation and the enhanced oxidation of LDL, is critical for the initiation and development of atherosclerosis In the early pathological stage, oxidized LDL (ox-LDL) induced expression of numerous adhesion molecules on the surface of vascular endothelial cells, which leads to increasing leukocyte adhesion and infiltration into the vessel wall. In addition, ox-LDL promotes vascular smooth muscle cell proliferation. Isothiocyanates (ITC) are organosulfur compounds rich in cruciferous vegetables. Previous studies have indicated that ITC are effective on protecting cardiovascular functions, inducing phase II detoxification enzyme expression, and promoting cancer cell apoptosis. In this study, we intend to elucidate the effect of benzyl isothiocyanate (BITC), phenylethyl isothiocyanate (PEITC) and sulforaphane (SFN) on ox-LDL-induced E-selectin expression in vascular endothelial cells and the molecular mechanisms involved. HUVEC were pretreated with 5 μM of BITC, PEITC or SFN for 24 h followed by exposing to 40 μg/ml ox-LDL for an additional 24 h. The results showed that (1) BITC, PEITC, and SFN pretreatment were effective on inhibiting ox-LDL-induced E-selectin expression; (2) three ITCs reduced the adherence of HL-60 to HUVEC; (3) intracellular heme oxygenase-1 (HO-1) expression was up-regulated by BITC, PEITC and SFN; (4) increase of intracellular reactive oxygen species (ROS) production by ox-LDL was suppressed by BITC, PEITC and SFN; (5) SFN significantly inhibited ox-LDL-induced ERK phosphorylation. Conclusion, results suggest that BITC, PEITC and SFN are effective on inducing HO-1 expression and, thus, ameliorating oxidative stress induced by ox-LDL, which in turn inhibit ERK activation and, finally, the expression of E-selectin in vascular endothelial cells. |
