中文摘要：

目的探讨卡托普利对动脉粥样硬化（AS）家兔血管内皮功能和形态的保护作用及其机制。方法采用高脂、高胆固醇饲料饲养家兔制备AS模型的同时口服给予卡托普利8mg·kg-1，每天1次，连续12周；HE染色观察血管组织形态，检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）；高效液相色谱测定血清非对称性二甲基精氨酸（ADMA）浓度；用重组编码人类二甲基精氨酸．二甲胺水解酶2（hDDAH2）基因的腺病毒感染AS家兔离体胸主动脉环2h，检测对乙酰胆碱累积浓度诱导的最大舒张反应（Emax）、半数有效量（EC50）及DDAH活性。结果与正常组比较，高脂模型家兔胸主动脉内膜和中膜增厚，血清TC，TG和LDL水平升高；血清ADMA浓度升高至（2．24±0．28）μmol·L-1（P〈0．01）；血管壁DDAH活性降至（0．048±0．007）U·g-1蛋白（P〈0．01）；Emax降低至（56±8）％（P〈0．01），EC50升高至（158±52）nmol·L-1（P〈0．01）。与As模型组比较，卡托普利治疗组血管内膜增厚减轻，血脂无明显降低，血清ADMA浓度显著降低至（1．37±0．23）μmol·L-1（P〈0．01），血管DDAH活性增加至（0．084±0．013）U·g-1蛋白（P〈0．01），内皮依赖性血管舒张功能改善，Emax增加至（88±4）％（P〈0．01），EC50降低至（90±35）nmol·L-1（P〈0．01）。AS模型血管转染DDAH2基因后，血管Emax回升至（88±4）％，EC50降低至（98±42）nmol·L-1，DDAH活性升高至（0．112±0．017）U·g-1蛋白，与卡托普利治疗组相似。结论卡托普利对AS家兔血管形态和内皮功能具有明显保护作用，其机制可能与增加血管DDAH活性，降低内源性ADMA浓度有关。

英文摘要：

OBJECTIVE To investigate the protective effects and mechanisms of captopril against vascular endothelial dysfunction and morphologic damage in atherosclerotic （AS） rabbits. METHODS The rabbits were fed a high-cholesterol and high-fat diets to induce AS, and at the same time treated with captopril （po 8 mg·kg-1） once daily for 12 week. The morphologic changes of thoracic aortas were observed by HE staining. Serum levels of total cholesterol （ TC）, triglycer- ides （TG）, low-density lipoprotein （LDL） and high-density lipoprotein （HDL） were determined. Serum levels of asymmetric dimethylarginine （ADMA） were assayed by high-pressure liquid chroma- tography. Recombinant human dimethylarginine dimethylaminohydrolase 2 （DDAH2） gene adenovi- ruses （AdSCMVhDDAH2） were ex vivo transferred to thoracic aortic tings from atherosclerotic rab- bits for 2 h. Endothelium-dependent maximal relaxation of aortic ring response to accumulative con- centrations of acetylcholine （ Emax ） , concentration for 50% of maximal effect （ EC50 ） and vascular DDAH activity were measured 24 h after transfection, respectively. RESULTS Compared with normal control group, the intima and media of thoracic aortas were thickened and serum lipid pro- files including TC, TG and LDL were obviously increased in rabbits fed high-fat diet. Serum ADMA levels were increased to （ 2.24 ＋- 0.28 ） μmol · L-1 （P 〈 0.01 ） and vascular DDAH activity was inhibited to （0. 048 ±0. 007） U· g-1 protein （P 〈 0.01 ） ; Emax was decreased to （56± 8 ） % （P 〈0.01 ） and EC50 was increased to （ 158 ±52） nmol·L-1 （P 〈0.01 ）. Treatment with captopril not only decreased vascular intima thickening and serum ADMA level to （ 1.37 ± 0.23 ） μmol· L- 1 （P 〈 0.01 ）, but also increased vascular DDAH activity to （0. 084± 0. 013 ） U · g-1 protein （P〈0.01） , Emax increased to （88±4） % （P〈0.01） and ECs0decreased to （90 ±35）nmol＇L-1 （ P 〈 0.01 ） without in