苯扎贝特逆转高甘油三酯血清下调内皮细胞一氧化氮合酶基因表达的机制探讨

Mechanisms of Bezafibrate Reverse Hypertriglyceridema Serum Down-regulating the Expression of Endothelial Nitric Oxide Synthase Gene in Cultured Bovine Endothelial Cells

目的研究苯扎贝特逆转高甘油三酯血清(HTS)下调原代牛主动脉内皮细胞(BVEC)一氧化氮合酶(eNOS)基因表达的可能机制。方法在前期研究证实HTS下调原代牛主动脉内皮细胞(BVEC)一氧化氮合酶(eNOS)蛋白质表达的基础上,采用Western印迹法检测苯扎贝特对HTS诱导的eNOS蛋白质表达水平下调的影响;在证实其效应的基础上研究其信号转导机制。结果发现苯扎贝特可以完全消除HTS对eNOS的抑制作用,经PPARα、PI3K、MAPKK和MAPK抑制剂预处理后,苯扎贝特逆转HTS下调eNOS的蛋白质表达的作用明显减弱。结论证实了苯扎贝特可以纠正HTS对eNOS的抑制作用,其效应的发挥既通过依赖于PPARα的方式,也可以经PI3K/MAPK/MAPKK信号通路介导。

Objective To study the mechanisms of bezafibrate reverse hypertriglyceridema serum（HTS） down-regulating the endithelial nitric oxide synthase（eNOS） expression in cultured primary bovine endothelial cells.Methods Based on the past results that HTS could down-regulate eNOS protein expression in cultured primary bovine endothelial cells,the effect of bezafibrate on the HTS down-regulating eNOS protein expression were detected by Western blot.Then the singal pathways were investigated by Western blot.Result Bezafibrate could attenuate the down-regulation effect of HTS on eNOS protein expression completely.Then these effects could be blocked by PPARα antagonist,PI3K,MAPKK and MAPK inhibitor.Conclusion Bezafibrate could attenuate the down-regulation effect of HTS on eNOS protein expression completely through PPARα dependent pathway and PPARα independent PI3K,MAPK and MAPKK pathways.