普罗布考对心脏微血管内皮细胞eNOS脱耦联与NADPH氧化应激途径的影响  

Effects of Probucol on AGEs-induced eNOS Uncoupling and NADPH Oxidative Stress Pathway

作　　者：成永霞[1,2] 郭素芬[1] 刘贵波[3] 冯玉宽[3] 颜彬[1] 王洪伟[1] 于建渤[1] 曹永[1] 李志强[1] 金在顺[1] 陈丽丽[4] 杨向红[5] 

机构地区：[1]牡丹江医学院病理教研室,157011 [2]黑龙江省高校肿瘤疾病防治重点实验室,牡丹江157011 [3]牡丹江医学院解剖教研室,157011 [4]牡丹江医学院附属红旗医院传染科,157011 [5]中国医科大学附属盛京医院病理科,沈阳100011

出　　处：《医药导报》2012年第8期975-979,共5页Herald of Medicine

基　　金：黑龙江省青年科学基金项目(QC2010040);黑龙江省2011年研究生创新科研资金项目(YJSCX2011-299HLJ);牡丹江医学院科学技术研究项目(2010-16)

摘　　要：目的观察普罗布考对心脏微血管内皮细胞内内皮型一氧化氮合酶(eNOS)脱耦联的作用,探讨其作用机制。方法 100 mg·L-1牛血清清蛋白糖基化终末产物(BSA-AGEs)与5,10,20μmol·L-1普罗布考作用于心脏微血管内皮细胞24 h,检测四氢生物喋呤(BH4)、一氧化氮(NO)和超氧阴离子(O2-),免疫组织化学检测eNOS蛋白表达情况,荧光染色检测活性氧簇(ROS),Western blot检测p47phox蛋白。结果随着普罗布考浓度增加,NO生成增加,O2-生成减少,eNOS表达减少,BH4含量增加,ROS表达降低,p47phox表达减少(P<0.01或P<0.05)。结论普罗布考能抑制AGEs诱导的心脏微血管内皮细胞eNOS脱耦联,其机制可能与抑制NADPH氧化应激有关。Objective To observe the effect of probucol on AGEs-induced eNOS uncoupling in cardiac microvascular endothelial cells,and to investigate its mechanism.Methods The cardiac microvascular endothelial cells were cultured in vitro.The cells were added with probucol（5,10 and 20 μmol·L^-1,respectively） and AGEs（100 mg·L^-1）,and incubated for 24 h.Meanwhile,a group managed with serum-free culture solution was assumed as blank control.We determined BH4,NO,O2-generation,eNOS,ROS and p47phox protein expression of all groups.Results As probucol concentration was increased,production of NO was increased gradually（P〈0.05）,production of O^2-decreased gradually（P〈0.05）,BH4 expression increased（P〈0.05）,eNOS expression gradually decreased（P〈0.05）,ROS was seen decreased gradually（P〈0.05）.Conclusion Probucol can inhibit intracellular eNOS uncoupling in the cardiac microvascular endothelial cells,and its mechanism might be related to suppressing the activation of NADPH oxidative stress pathway.

关 键 词：普罗布考 糖基化终末产物 血管内皮细胞 一氧化氮 

分 类 号：R972[医药卫生—药品] R965[医药卫生—药学]