辛伐他汀通过上调sirt1抵抗氧化低密度脂蛋白诱导的内皮细胞衰老

Anti-aging Effects of Simvastatin on ox-LDL Induced Endothelial Cells Via Upregulation of SIRT1

目的:探讨辛伐他汀对氧化低密度脂蛋白诱导的内皮细胞衰老的作用及其可能机制。方法:体外培养人脐静脉内皮细胞,给予不同浓度(0、25、50、100μg/ml)氧化低密度脂蛋白(ox-LDL)培养24小时,观察细胞β-半乳糖苷酶染色及SIRT1蛋白表达的变化;给予不同浓度辛伐他汀(1、5、10μmol/L)预处理内皮细胞1小时后加入100μg/ml ox-LDL培养人脐静脉内皮细胞23小时,检测细胞β-半乳糖苷酶染色及SIRT1蛋白表达的变化。结果:随着ox-LDL作用浓度的增加,细胞内β-半乳糖苷酶染色的阳性细胞百分率逐渐升高,与空白对照组相比差异均有统计学意义(P<0.05),在ox-LDL(100μg/mll)组达到最高,显著高于ox-LDL(25μg/ml)组(P<0.001)。而不同浓度ox-LDL处理的细胞内SIRT1的表达较空白对照组相比逐渐下降,ox-LDL(50、100μg/ml)组SIRT1的表达显著低于ox-LDL(25μg/ml)组(P<0.05)。10μmol/L辛伐他汀预处理能明显降低100μg/ml ox-LDL处理的内皮细胞内β-半乳糖苷酶染色的阳性细胞百分率(P<0.001),并显著抑制细胞内SIRT1的蛋白表达(P<0.001)。结论:辛伐他汀可以抵抗ox-LDL诱导的内皮细胞衰老,可能与增加内皮细胞内SIRT1的表达有关。

Objective： To investigate the anti-aging effects and mechanisms of simvastatin on ox-LDL induced endothelial cells. Methods： Human umbilical vein endothelial cells were cultured and incubated with different concentrations （0,25,50,100 μg/ml）of ox-LDL for 24 hours, and [3-galactosidase staining results and SIRT1 protein expression were observed. Different concentrations of simvastatin （1,5,10 μmol/L）were added to ox-LDL （100μg/ml） -treated human umbilical vein endothelial cells, and changes in the [3-galactosidase staining results and expressions of SIRT1 protein were observed as well. Results： With the increase of concentrations of ox-LDL, the percentage of positive Beta galactosidase staining of cells were gradually increased （P〈0.05）. which was significantly higher than that in the control group and highest in 100 ~Lg/ml ox-LDL induced endothelial cellls （P〈0.05）, it was significantly higher than that in 25 ~Lg/ml ox-LDL （P〈0.001）. The expression of SIRT1 in cells treated with different concentrations of ox-LDL decreased gradually in comparison with the control group, which was significantly lower in 50, 100 μg/ml ox-LDL group than that in ox-LDL group （P〈0.05）. Pretreatment of simvastatin （10 μM） significantly decreased the percentage of positive β-galactosidase staining in endothelial cells induced by 100 μg/ml ox-LDL （P〈0.001）, and significantly inhibited the expression of SIRT1 （P〈0.001）. Conclusion： Simvastatin could inhibit ox-LDL-induced aging in endothelial cell, and the increase of expression of SIRT1 was possibly involved.