金雀异黄素对低密度脂蛋白氧化修饰及氧化型低密度脂蛋白诱导的血管内皮细胞c-myc mRNA表达的抑制作用  

Inhibitory Effects of Genistein on the Oxidative Modification of Low Density Lipoprotein and c-myc mRNA Expression Induced by Oxidized Low Density Lipoprotein in Vascular Endothelial Cells

作　　者：刘锦[1] 鲁映青[1] 

机构地区：[1]复旦大学上海医学院药理学系,上海市200032

出　　处：《中国动脉硬化杂志》2002年第6期509-512,共4页Chinese Journal of Arteriosclerosis

摘　　要：为探讨大豆异黄酮 (金雀异黄素和大豆甙元 )在防止低密度脂蛋白氧化方面的作用以及对氧化型低密度脂蛋白诱导的血管内皮细胞原癌基因c myc表达的影响 ,采用Cu2 + 介导的低密度脂蛋白体外氧化方法 ,通过测定硫代巴比妥酸反应物质生成和琼脂糖电泳迁移率的变化来观察大豆异黄酮对低密度脂蛋白氧化修饰的抑制作用 ;采用Northernblot杂交技术 ,分析氧化型低密度脂蛋白对人脐静脉内皮细胞c myc原癌基因mRNA表达的作用以及金雀异黄素对此表达的影响。结果发现 ,金雀异黄素能够浓度依赖性减少硫代巴比妥酸反应物质生成 ,降低低密度脂蛋白的相对电泳迁移率 (P <0 .0 5 ) ;氧化型低密度脂蛋白 (2 0 0mg L)刺激人脐静脉内皮细胞c mycmRNA在 1～ 2h内表达增高 ,表达量为对照水平的 3倍 ,4h回到对照水平以下 ;金雀异黄素 (10 0 μmol L)能有效抑制氧化型低密度脂蛋白诱导的c mycmRNA表达增高。以上结果提示 ,金雀异黄素不仅能防止低密度脂蛋白发生氧化 ,而且能够抑制氧化型低密度脂蛋白诱导的人脐静脉内皮细胞cAim To discuss the effect of soy isoflavones (Genistein and Daidzein) on preventing the oxidation of LDL mediated by Cu 2+ and to investigate the effect of Genistein on c myc mRNA expression induced by ox LDL in human vascular endothelial cells (ECV304). Methods 1. LDL were isolated from healthy human plasma by gradient ultra centrifugation and oxidized by Cu 2+ . The formation of TBARS and relative electrophoretic mobility were employed to measure the antioxidant activity of Genistein and Daidzein of different concentrations (50, 100 and 200 μmol/L respectively). 2. LDL isolated from healthy human plasma by gradient ultra centrifugation and oxidized by Cu 2+ was used as a stimulus. ECV304 cells were exposed to ox LDL (200 mg/L) in the presence or absence of Genistein 100 μmol/L for 1, 2 and 4 h in vitro. Northern Blot was employed to measure c myc mRNA levels of the treated cells. Results 1. The formation of TBARS and relative electrophoretic mobility of LDL were inhibited by Genistein in a concentration dependent manner (P<0.05 vs control); However, Daidzein made none senses compared with control on the formation of TBARS and relative electrophoretic mobility of LDL (P>0.05). 2. In response to ox LDL 200 mg/L, c myc mRNA expression of hUVEC increased by about three folds in 1 2 h and decreased below the control level at 4 h; Genistein 100 μmol/L effectively inhibited this over expression both at 1 and 2 h. Conclusions Genistein not only prevents the oxidation of LDL but also inhibits the over expression of c myc mRNA induced by ox LDL in ECV304.

关 键 词：金雀异黄素 大豆甙元 低密度脂蛋白 血管内皮 C-MYC 原癌基因 

分 类 号：R363.1[医药卫生—病理学]