普罗布考、厄贝沙坦对人脐静脉内皮细胞氧化应激损伤的保护作用及PAI-1含量的影响

目的探讨抗氧化剂普罗布考、AT1受体拮抗剂厄贝沙坦对人脐静脉内皮细胞(HUVEC)氧化损伤及PAI-1含量的影响。方法采用H2O(2100μmol/L)制作氧化应激损伤的细胞模型,给予不同浓度普罗布考、厄贝沙坦预孵育细胞:(1)空白对照组;(2)H2O2组;(3)Pro1组:H2O2+普罗布考(2.5μmol/L);(4)Pro2组:H2O2+普罗布考(5μmol/L);(5)Pro3组:H2O2+普罗布考(10μmol/L);(6)Irb1组:H2O2+厄贝沙坦(2.5μmol/L);(7)Irb2组:H2O2+厄贝沙坦(5μmol/L);(8)Irb3组:H2O2+厄贝沙坦(10μmol/L);(9)Pro3+Irb3组:H2O2+普罗布考(10μmol/L)+厄贝沙坦(10μmol/L)。用MTT法检测普罗布考及厄贝沙坦对HUVEC氧化损伤的影响;用ELISA方法测定培养液中PAI-1含量。结果 MTT:空白对照组、Pro2组、Pro3组、Irb3组、Pro3+Irb3组吸光度值高于H2O2组(空白对照组、Pro2组、Pro3组、Pro3+Irb3组P0.01,Irb3组P0.05);空白对照组、Irb1组、Irb2组和Irb3组培养液中PAI-1均高于H2O2组(空白对照组、Irb2组、Irb3组P0.01;Irb1组P0.05);与Pro+Irb组比较,H2O2组、Pro3组细胞培养液中PAI-1水平均较高(P0.01)。结论普罗布考和厄贝沙坦可通过不同机制减轻氧化应激对HUVEC的影响,从而对血管内皮细胞产生保护作用;二者在改善氧化应激引起的PAI-1水平升高方面存在一定的协同作用。

Effect of Probucol and Irbesartan on Oxidative Stress Injury and PAI-1 of HUVEC

Objective To investigate the effect of probucol and irbesartan on oxidative stress injury and PAI-1 of HUVEC.Methods The endothelium cell model of oxidative stress was made by H2O2（100 μmol/L）,the model cells was divided into 9 groups and treated with different concentration of probucol or irbesartan：（1）placebo;（2）H2O2;（3）Pro1：H2O2＋probucol（2.5 μmol/L）;（4）Pro2：H2O2＋probucol（5 μmol/L）;（5）Pro3：H2O2＋probucol（10 μmol/L）;（6）Irb1：H2O2＋irbesartan（2.5 μmol/L）;（7）Irb2：H2O2＋ irbesartan（5 μmol/L）;（8）Irb3：H2O2＋irbesartan（10 μmol/L）;（9）Pro3＋Irb3：H2O2＋probucol（10 μmol/L）＋irbesartan（10 μmol/L）.The effect of probucol and irbesartan on oxidative stress injury of HUVEC were measured by MTT,the level of PAI-1 of the cell culture fluid were measured by ELISA.Results The OD of C,Pro2,Pro3,Irb3,and Pro3＋Irb3group were higher than that of H2O2 group（C,Pro2,Pro3,Pro3＋Irb3 P〈0.01,Irb3 P〈0.05）.The level of PAI-1in culture fluid of C,Irb1,Irb2 and Irb3group were higher than that of H2O2 group（C,Irb2,Irb3 P〈0.01,Irb1 P〈0.05）.Compared to Pro＋Irb group,the level of PAI-1 in culture fluid of H2O2 and Pro3 group were higher（P〈0.01）.Conclusion Probucol and irbesartan could increase the clearance of oxygen radicals in endothelium,and then protected the normal function of endothelium.They maybe have some kind of synergistic reaction on improvement of the increased level of PAI-1 caused by oxidative stress.