银杏内酯B对内皮细胞的保护作用及分子机制研究

目的探讨银杏内酯B对氧化型低密度脂蛋白刺激脐静脉内皮细胞保护作用的分子机制。方法分别用银杏内酯B 0.2、0.4、0.6 g.L-1预孵育内皮细胞1 h,再加入ox-LDL(0.1 g.L-1)刺激细胞。用Western blot检测Lectin-likeoxidized LDL receptor-1(LOX-1)、PI3K、Nrf2、SIRT1表达及Akt磷酸化。结果 1.ox-LDL刺激内皮细胞LOX-1表达增加,银杏内酯B以剂量依赖方式抑制了LOX-1表达。2.银杏内酯B有效地抑制了ox-LDL刺激的Akt磷酸化,但对PI3K的表达无影响。3.ox-LDL刺激内皮细胞SIRT1表达降低,银杏内酯B有意义地增加了细胞SIRT1表达。4.ox-LDL刺激细胞抗氧化应激蛋白Nrf2表达明显增加,银杏内酯B下调了Nrf2的表达。结论银杏内酯B对内皮细胞保护作用与抑制LOX-1表达、Akt磷酸化,启动细胞内源性保护机制相关。

Protective effect of ginkgolide B on ox-LDL stimulated endothelial cells

Aim To investigate the effect of ginkgolide B on ox-LDL stimulated human umbilical vein endothelial cells(HUVECs).Methods After incubation with ginkgolide B(0.2,0.4,0.6 g·L-1) for 1 h,cells were treated with ox-LDL(0.1 g·L-1) for 4 h.The expressions of lectin-like oxidized LDL receptor-1(LOX-1),Nrf2,PI3K,SIRT1 and Akt phosphorylation were analyzed with Western blot.Results The expression of LOX-1 was increased in ox-LDL-treated HUVECs.In contrast,ginkgolide B significantly decreased the LOX-1 expression.Ginkgolide B attenuated Akt phsphorylation in ox-LDL-treated cells in a dose-dependent manner,but it had no effect on PI3K expression.SIRT1 expression was down-regulated in ox-LDL stimulated cells,whereas ginkgolide B significantly increased SIRT1 expression.Nrf2 expression was up-regulated in cells treated with ox-LDL,and ginkgolide B restored the change of Nrf2 expression significantly.Conclusion Ginkgolide B has protective effects on ox-LDL stimulated endothelial cells,and the mechanism might be associated with reductiion of LOX-1 expression,inhibition of Akt phosphorylation and onset of intracellular protective signaling molecule.