口服巯基供体改善动脉粥样硬化兔硝酸酯耐药的实验观察  

Experimental study on the prevention of nitrate tolerance in rabbits with atherosclerosis by oral administration of sulfhydryl donor

作　　者：陈良[1] 蒋锦琪[1] 冯辉[1] 

机构地区：[1]上海交通大学附属胸科医院急诊科,上海200030

出　　处：《中国循证心血管医学杂志》2017年第12期1449-1451,1454,共4页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：中国医师协会探索心血管研究基金(DFCMDA201431)

摘　　要：目的探讨巯基供体N-乙酰半胱氨酸(NAC)对动脉粥样硬化模型兔硝酸酯耐药的影响及相关机制。方法选择40只雄性新西兰大白兔,随机分为正常组、模型组(AS组)、硝酸酯组(ISMN组)、硝酸酯耐药组(NT组)和用药组(NT+NAC组),各8只。除正常组,其他各组通过球囊内皮剥脱联合高脂饮食建立腹主动脉粥样硬化模型。高脂饲料饲养8周后,ISMN组灌胃给予ISMN 25 mg,1/24 h;NT组灌胃ISMN 25 mg,1/12 h;NT+NAC组则同时灌胃ISMN 25 mg和NAC 100 mg,1/12 h;AS组和正常组不予干预。用药7 d后,取腹主动脉,分别进行病理学观察、血管环舒张反应检测以及血管总巯基(T-SH)、超氧阴离子(·O2-)、超氧化物歧化酶(SOD)、丙二醛(MDA)、内皮素-1(ET-1)和亚硝酸盐(NO2-)测定。结果各建模组HE染色后,均可见内膜不同程度的增厚,大量泡沫细胞、平滑肌细胞和脂质沉积。各组血管环的舒张幅度均随硝酸甘油(NTG)浓度的增加而递增。当NTG为10-9 mol/L时,NT组血管舒张幅度则显著低于其余四组,差异有统计学意义(P均<0.05)。当NTG浓度为10-8~10-4mol/L时,与正常组比较,AS组、ISMN组、NT组以及NT+NAC组血管舒张幅度均降低,差异有统计学意义(P均<0.05);NT组血管舒张幅度则显著低于其余四组,差异均有统计学意义(P均<0.05)。T-SH含量由高至低依次为正常组、AS组、NT+NAC组、ISMN组以及NT组,各组间比较差异均有统计学意义(P均<0.05)。·O2-、MDA、ET-1和NO2-含量:正常组、AS组、NT+NAC组、ISMN组、NT组呈升高趋势,除正常组与AS组外,其余各组间比较差异均有统计学意义(P均<0.05)。NT组SOD含量低于正常组,且NT+NAC组SOD含量高于NT组,差异均有统计学意义(P均<0.05)。结论口服N-乙酰半胱氨酸可通过补充巯基、抑制氧化应激来改善动脉粥样硬化兔硝酸酯耐药的效应。Objective To investigate the preventive value and mechanism of oral administration of sulfhydryl donor, N-acetylcysteine （NAC）, on nitrate tolerance in rabbits with atherosclerosis （AS）. Methods Abdominal aorta atherosclerosis models in 32 adult male New Zealand white rabbits were established by balloon denudation combined with high-fat diet. All rabbits were randomly divided into control group （AS group）, nitrate group （ISMN group）, nitrate tolerance group （NT group） and combination treatment group （NT＋NAC group） （with 8 animals in each group）. In AS group, no drugs were administrated. In ISMN group, isosorbide-5-mononitrate （ISMN） was administrated by gastric tube at the dose of 25 mg/ 24 h. In NT group, ISMN was administrated at the dose of 25 mg/12 h. And in NT＋NAC group, combination drugs of ISMN （25 mg/12 h） and NAC （100 mg/12 h） were administrated. After 7 days of administration, abdominal aortas removed from all animals were cut into several 5 mm long segments for pathological observation, detection of vascular ring diastolic reaction, and measurement of the levels of total sulfhydryls （T-SH）, superoxide anion （·O2-）, superoxide dismutase （SOD）, malondialdehyde （MDA） and endothelin-1 （ET-1）. Results The abdominal aorta atherosclerosis models were successfully established in all rabbits. Vascular ring diastolic reaction in NT group was significantly weaker than that in other groups （P〈 0.05）. While in NT＋NAC group, the vascular ring diastolic reaction was notably stronger than that in NT group （P〈0.05） but was similar to that in AS group and ISMN group （P〉0.05）. The levels of ·O2-、MDA、ET-1 and NO2- in vascular tissues were respectively the highest in NT group, then in ISMN group, then in NT＋NAC group, and the lowest in AS group. There was significant difference in each parameter among 4 groups （P〈0.01） except in ·O2- level between AS group and NT＋NAC group （P〉0.05）. On the contrary, the levels of

关 键 词：硝酸酯耐药 巯基 5-单硝酸异山梨醇酯 N-乙酰半胱氨酸 

分 类 号：R543.5[医药卫生—心血管疾病]