大豆異黃酮genistein與daidzein對α腫瘤壞死因子所誘導人類主動脈內皮細胞發炎反應之影響

Effect of Genistein and Daidzein on Inflammatory Response in TNF-α-treated Human Aortic Endothelial Cells

氧壓與發炎反應是影響動脈粥狀硬化形成最重要的因素與促進者，由於影響血管內皮黏附分子的表現，在動脈粥狀硬化形成和慢性發炎中扮演重要角色。許多研究顯示膳食補充大豆食品可降低心血管疾病，尤其是大豆含有豐富的異黃酮，主要以genistein 、daidzein 為主，具有良好的抗氧化能力。本研究主要探討大豆異黃酮genistein 和daidzein 對前發炎細胞激素腫瘤壞死因子（TNF-α ）誘導人類主動脈內皮細胞（human aortic endothelial cells ；HAECs） 發炎反應的影響。隨著HAECs 處理geni stein 和daidzein 的濃度增加， 而能明顯的抑制TNF-α 誘發HAECs 對單核球（U937） 的吸附能力， 濃度為150μM genistein 時， 吸附能力只剩48.2±8.0% ；濃度為150μM daidzein 時，為47.2±4.9% ；利用西方墨點法（wes tern blot） 分析HAECs 黏附分子的表現， 當處理geni stein 濃度為100μM 及150μM 時， TNF-α 誘發HAECsVCAM-1 表現量為49.9±6.3% 及34.6±6.0% ，當daidzein 濃度為100μM 及150μM 時，VCAM-1 表現量為93.7±1.1% 及88.5±1.7% ；而在geni stein 濃度為100μM 及150μM 時， ICAM-1 表現量為71.5±3.3% 及37.1±4.7% ， daidzein 濃度為100μM 及150μM 時， ICAM-1 為70.9±4.6% 及68.9±0.1% 。綜合研究顯示genistein 及daidzein 能有效的抑制TNF- α誘發HAECs 表現黏附分子，因而降低HAECs 對單核球的吸附能力，有助於減緩發炎反應及動脈粥狀硬化的進展。

Oxidative stress and inflammation are regarded as crucial contributors and promoters of arteriosclerosis. In addition, the altered expression of cell-adhesion molecules by the arterial endothelium plays a major role during arteriosclerosis and chronic inflammation. Several studies have demonstrated that including soy-based foods as part of dietary intakes is associated with reduced cardiovascular risk. Specifically, soybeans are rich in isoflavones (genistein and daidzein). Antioxidants may modulate oxidative stress, which in turn may trigger intracellular signaling pathways that can influence the expression and atherogenesis gene and adhesion molecules. Anti-inflammatory research has indicated that TNF-α can induce the production of human aortic endothelial cells (HAECs), resulting in an inflammatory reaction. Investigations into the effect of adhesion to the HAECs by genistein and daidzein in monocytes (U937) indicated that the adhesion of monocytes on HAECs was inhibited, and the genistein and daidzein concentrations increased. Western blot was used to analyze genistein and daidzein in HAECs on TNF-α to induce the production of cell -adhesion factors VCAM-1 and ICAM-1. The results suggested that the inhibition effect of genistein is more effective than that of daidzein. Both genistein and daidzein showed adhesion-factor performance, as induced by anti-oxidation and anti-inflammatory reactions. These isoflavones could therefore have a substantial effect on the prevention of arteriosclerosis, and play a prominent role in further research into the anti-inflammatory mechanism.