普罗布考和辛伐他汀对高级糖基化终末产物诱导的大鼠肾脏微血管内皮细胞的ROS含量和HO-1表达影响  

Effect of probucol and simvastatin on reactive oxygen species production and HO-1 expression induced by advanced glycation end products in rat renal microvascular endothelial cells

作　　者：王哲[1] 马铁[2] 杨向红[2] 

机构地区：[1]中国医科大学附属盛京医院输血科,辽宁沈阳110004 [2]中国医科大学附属盛京医院病理科,辽宁沈阳110004

出　　处：《中国病理生理杂志》2010年第9期1749-1752,共4页Chinese Journal of Pathophysiology

摘　　要：目的:探讨普罗布考和辛伐他汀对高级糖基化终末产物(AGEs)诱导的大鼠肾脏微血管内皮细胞(RMECs)活性氧(ROS)含量和血红素氧合酶-1(HO-1)表达的影响。方法:体外分离和培养RMECs,将其分为对照组、AGEs损伤组、普罗布考组和辛伐他汀组;2',7'二氯荧光黄双乙酸盐(DCFH-DA)荧光染色检测各组细胞中ROS含量;逆转录聚合酶链反应法及Westernblotting检测各组细胞血红素氧合酶-1(HO-1)mRNA水平和蛋白表达。结果:(1)AGEs能上调RMECs中ROS生成和HO-1表达(P<0.05或P<0.01)。(2)普罗布考能上调RMECs中HO-1表达,能下调AGEs诱导RMECs中ROS生成和HO-1表达(P<0.05或P<0.01)。(3)辛伐他汀能下调AGEs诱导细胞ROS含量增加,但对RMECs中HO-1表达无明显影响(P>0.05)。结论:普罗布考对AGEs诱导下RMECs保护作用机制可能与其能下调内皮细胞HO-1表达有关;而同样具有抗氧化保护肾脏作用的辛伐他汀对AGEs诱导的RMECs的HO-1表达的影响不大。AIM： To investigate the effect of probucol and simvastatin on the production of reactive oxygen species （ ROS） and heme oxygenase-1 （ HO-1） expression induced by advanced glycation end products （ AGEs） in rat renal microvascular endothelial cells （ RMECs） . METHODS： RMECs isolated and cultured from rat kidney were divided into 4 groups： normal control group,AGEs group,probucol group and simvastatin group. The levels of ROS were determined by the molecular probes of DCFH-DA. The expression of HO-1 at mRNA and protein levels was detected by RT-PCR and Western blotting,respectively. RESULTS： （ 1） AGEs up-regulated ROS production and HO-1 expression in RMECs. （ 2） Probucol up-regulated HO-1 expression in RMECs,and inhibited the increasing level of ROS and expression of HO-1 in RMECs induced by AGEs. （ 3） Simvastatin also inhibited the increasing level of ROS in RMECs induced by AGEs,but it had no effect on HO-1 expression in RMECs with or without AGEs. CONCLUSION： Protective effect of probucol on the dysfunction of RMECs induced by AGEs may be related with its effect on the expression of HO-1 at mRNA and protein levels. Simvastatin also plays roles in antioxidation and renal protection,but is ineffective in the modulation of HO-1 expression.

关 键 词：普罗布考 辛伐他汀 糖基化终产物 高级 血红素氧化酶-1 氧化性应激 

分 类 号：R363[医药卫生—病理学]