普罗布考对高同型半胱氨酸血症大鼠血管功能的保护作用  

Protective effects of Probucol on endothelial function in rats with hyperhomocysteinemia

作　　者：高胜利[1] 李莉[2] 翟晓娟[2] 郭任维[2] 燕子[3] 高淑红[4] 

机构地区：[1]山西医科大学汾阳学院生理学教研室,山西汾阳032200 [2]山西医科大学附属汾阳医院心血管内科,山西汾阳032200 [3]山西医科大学生理学系,山西太原030001 [4]山西医科大学汾阳学院统计学教研室,山西汾阳032200

出　　处：《中国医药导报》2015年第25期23-26,共4页China Medical Herald

摘　　要：目的探讨普罗布考对高同型半胱氨酸血症大鼠内皮功能的作用及机制。方法30只大鼠随机分为3组，对照组（10只）基础饲料饲养，高同型半胱氨酸血症（HHcy）组（10只）在基础饲料上添加3％L-蛋氨酸喂养4周，普罗布考组（10只）高蛋氨酸饲料喂养4周，同时给予普罗布考150mg／d灌胃。喂养4周时检测各组大鼠胸主动脉血管内皮依赖性舒张功能、血浆一氧化氮（NO）、非对称性二甲基精氨酸（ADMA）含量和内皮型一氧化氮合酶（eNOS）活性，胸主动脉二甲基精氨酸二甲氨基水解酶（DDAH2）活性和蛋白质表达。结果HHcy组大鼠同型半胱胺酸（Hcy）含量显著升高，与HHcy组比较，普罗布考组大鼠Hcy含量降低（P〈0．01）。给予1×10^-7～1×10^-5mol／L累积浓度的乙酰胆碱后，HHcy组大鼠血管张力低于对照组和普罗布考组（P〈0．05）；给予1×10^-8～1×10^-4mol／L累积浓度的酸化亚硝酸钠（NaNO2）后，三组间的血管张力无明显差别（P〉0．05）。与对照组比较，HHcy组大鼠血浆NO含量降低（P〈0．05），eNOS活性降低（P〈0．01），ADMA含量增高（P〈0．05），胸主动脉DDHA2活性降低（P〈0．01）和蛋白质水平降低（P〈0．01）；与HHcy组比较，普罗布考组大鼠血浆NO含量增高（P〈0．01），eNOS活性增高（P〈0．05），ADMA含量降低（P〈0．01），胸主动脉DDHA2活性增高（P〈0．01）和蛋白质水平增高（P〈0．05）。结论普罗布考能降低高同型半胱氨酸血症大鼠血浆Hcy水平，改善动脉内皮依赖性舒张功能。其机制与DDAH／ADMA／NOS／NO通路有关。Objective To investigate the effect and mechanism of Probucol on endothelial function in hyperhomocys- teinemia rats. Methods 30 rats were randomly divided into three groups. Control group （10 rats） were feed in the basal diet; HHcy group （10 rats） in the basal diet added 3% L-methionine diet for 4 weeks; Probucol group （10 rats） of high methionine diet for 4 weeks, and was treated with Probucol 150 mg/d orally. Thoracic aortic EDD, plasma NO, ADMA content and eNOS activity of rats in each group were detected in 4 weeks; DDAH2 activity and protein expression in thoracic aorta were detected in 4 weeds. Results The content of Hcy in the rats of the HHcy group increased significantly, compared with the HHcy group, the Hcy content in the Probucol group rats was decreased （P 〈 0.01）. Given 1×10^-7～1×10^-5mol/L Cumulative concentration of ACh, vascular tension in HHcy group rats were lower than control group and Probucol group （P 〈 0.05）; after given the cumulative concentration NaNO2 1×10^-8～1×10^-4mol/L, vascular tension between the three groups had no difference （P 〉 0.05） . Compared with the control group, plasma NO content was reduced （P 〈 0.05）, eNOS activity was lower （P 〈 0.01）, the ADMA content was increased （P 〈 0.05）, aortic DDHA2 activity was decreased （P 〈 0.01） and protein level was decreased in HHcy group （P 〈 0.01）. Compared with HHcy group, plasma NO content were increased （P 〈 0.01）, eNOS activity was increased （P 〈 0.05）, the ADMA content were decreased （P 〈 0.01）, the thoracic aortic DDHA2 activity was increased （P 〈 0.01） and protein level was increased （P〈 0.05）in Probucol group. Conclusion Probucol can reduce the level of plasma Hey in hyperhomoeysteinemia rats, improve thoracic aorta endothelial dependent diastolic function, its mechanism is related to the DDAH/ADMA/NOS/NO pathway.

关 键 词：普罗布考 同型半胱氨酸 内皮依赖性舒张功能 一氧化氮 内皮型一氧化氮合成酶 非对称二甲基精氨酸 二甲基精氨酸二甲胺水解酶2 

分 类 号：R589.2[医药卫生—内分泌]