The analysis of the mechanism of the anti-atherogenic action of polyphenol utilizing new evaluation technology

由于大豆异黄酮类化合物的结构与雌激素相似，且具有雌激素样活性，因此大豆异黄酮类化合物对动脉粥样硬化、癌症、骨质疏松症的治疗作用已被广泛报道。据报道，血清中抗动脉粥样硬化因子载脂蛋白A-I(ApoA-I)水平的变化受雌激素、异黄酮类等激素的影响。关于异黄酮类化合物对载脂蛋白A-I基因表达影响的研究报道较少。因此，本研究探讨了大豆异黄酮类、金雀异黄素对载脂蛋白A-I及其mRNA水平的影响，并探讨了金雀异黄素对载脂蛋白A-I基因表达的作用机制。与对照组相比，染料木素可显著增加HepG2细胞分泌载脂蛋白A-I的水平。与对照组相比，金雀异黄素可显著上调HepG2细胞载脂蛋白A-I的mRNA水平。在转导雌激素受体a的HepG2细胞中，金雀异黄素显著上调载脂蛋白A-I基因转录。将雌激素受体α和ApoA-I突变的启动子CAT质粒(-264~-191缺失CAT质粒和-80~40缺失CAT质粒)同时导入肝癌细胞，与对照组相比，金雀异黄素对ApoA-I基因转录无明显影响。我们首次发现金雀异黄素通过雌激素受体α和-264~-191和-80~-40反式激活载脂蛋白A-I基因的表达。

As the structure of the isoflavonoids is similar to that of estrogen and isoflavonoids has a estrogenic activity, the beneficial effects of dietary soy isoflavonoids on atherosclerosis, cancer, osteoporosis has been extensively reported. As it is reported that the serum level of the antiatherogenic factor, apolipoprotein A-I (ApoA-I) changes by hormone such as estrogen, isoflavonoids is expected to have its effects. There is few reports that the effects of isoflavonoids on the ApoA-I gene expression. Thus, in the present study, we investigate that the effects of soy isoflavonoids, genistein on the level of ApoA-I and its mRNA, the mechanism of genistein action on the ApoA-I gene expression. The secreted ApoA-I level is significantly increased by genistein compared to control in HepG2 cells. The mRNA level of ApoA-I is significantly increased by genistein compared to control in HepG2 cells. In estrogen receptor a tranfected HepG2 cells, the ApoA-I gene transcription is significantly increased by genistein compared to control. The transfection of both estrogen receptor α and the ApoA-I mutated promoter CAT plasmids (-264〜-191 deleted CAT plasmid and -80-40 deleted CAT plasmid) into HepG2 cells, the ApoA-I gene transcription is unchanged by genistein compared to control.We found for the first time that genistein increased ApoA-I and its mRNA levels, and transactivated the ApoA-I gene expression through estrogen receptor α and -264〜-191 and -80〜-40 in the ApoA-I gene promoter.