氧自由基在一氧化氮缺乏所致高血压及心血管重构中的作用(英文)  

Role of oxygen free radicals in hypertension and cardiovascular remodeling of nitric oxide-deficient rats

作　　者：陈琦[1] 吴延庆[1] 程晓曙[1] 邹斌[1] 吴清华[1] 苏海[1] 李菊香[1] 

机构地区：[1]南昌大学第二附属医院心血管内科,南昌大学心血管疾病研究所,江西省南昌市330006

出　　处：《中国临床康复》2006年第44期198-201,共4页Chinese Journal of Clinical Rehabilitation

基　　金：江西省自然科学基金(0040045)~~

摘　　要：背景:以往研究表明,心肌及血管局部组织中的肾素-血管紧张素系统激活参与了高血压及心血管重构的形成过程,但其是否通过氧自由基发生作用尚不明确。目的:观察抗氧化剂依布硒啉对长期给予一氧化氮合酶抑制剂硝基精氨酸甲酯大鼠的干预效果,分析氧自由基在一氧化氮缺乏所致高血压、心血管系统重构中的作用。设计:随机分组,对照动物实验。单位:南昌大学第二附属医院心血管内科,南昌大学心血管疾病研究所。材料:实验于2002-01/2003-03在南昌大学心血管病研究所动物实验室及医学分子中心实验室完成。选择雄性Wistar大鼠24只,按随机数字表法分为3组,每组各8只,即正常对照组、一氧化氮合酶抑制剂组和一氧化氮合酶抑制剂+依布硒啉组。方法:①正常对照组:常规饮食饮水,给予4g脱脂奶球。②一氧化氮合酶抑制剂组:将硝基精氨酸甲酯50mg/(kg·d)添加于4g脱脂奶球中喂食。③一氧化氮合酶抑制剂+依布硒啉组:将硝基精氨酸甲酯50mg/(kg·d)及依布硒啉30mg/(kg·d)分别添加于2g脱脂奶球中喂食。在大鼠给予硝基精氨酸甲酯前和喂药后1,2,4,6,8周末测收缩压。8周末麻醉后处死大鼠,取血浆及心尖部心肌匀浆测生化指标,其余心脏组织行病理学检测。主要观察指标:①各组大鼠血压动态变化情况。②各组大鼠血浆、心肌组织一氧化氮水平、超氧化物歧化酶及血管紧张素转换酶活性、心肌超氧阴离子生成率及心肌血管紧张素Ⅱ1型受体蛋白表达水平。③各组大鼠病理形态学检测指标。结果:24只大鼠全部进入结果分析,无脱失。①各组大鼠收缩压:给药后第1,2,4,6,8周末一氧化氮合酶抑制剂组大鼠收缩压逐渐升高,显著高于正常对照组同期收缩压(P<0.05～0.01);在给药后第8周末,一氧化氮合酶抑制剂+依布硒啉组收缩压显著低于一氧化氮合酶抑制剂组(P<0.05)。②各组大鼠血�BACKGROUND： Our previous study showed that the activation of local renin-angiotensin system in heart and vessels contributed to hypertension and cardiovascular remodeling. However, whether oxygen free radical plays an important role in this process is still unclear. OBJECTIVE： To investigate the interventional effects of Ebselen, a kind of anti-oxidative drug, on rats administered by Nw-Nitro-L-arginine methyl easter （L-NAME） （L-NAME）, inhibitor of nitric oxide synthase （NOS） for a long term, and probe into the role of oxygen free radicals （OFR） in hypertension and cardiovascular remodeling of NO-deficient rats. DESIGN： A randomized grouping and controlled animal trial. SETTING： Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Institute of Cardiology, Nanchang University. MATERIALS： The experiment was completed from January 2002 to March 2003 at the Animal Experimental Lab, Institute of Cardiology, Nanchang University and the Key Molecular Medical Lab of Jiangxi Province. Twenty-four Wistar rats were divided to three gr3ups according to the random number table method： normal control group （n=8）, L-NAME group （n=8）, L-NAME ＋ Ebselen group （n=8）. METHODS： （1）Normal control group： The rats could eat and drink routinely, and they were administrated by skim milk ball （net weigh = 4 g） before feed every night. （2） L-NAME group： The rats received L-NAME in the dose of 50 mg/kg mixed in one skim milk ball everyday before feed every night. （3） L-NAME ＋ Ebselen group： The rats were administered by one skim milk ball （net weigh = 2 g） mixed with L-NAME （50 mg/kg） and one skim milk ball （net weigh = 2 g） mixed with ebselen （30 mg/kg）. The systolic blood pressure （SBP） was detected before L-NAME was given and at the ends of the 1^st, 2^nd, 4^th, 6^th and 8^th weeks respectively. The rats were killed under anesthesia at the end of the 8^th week, the plasma and homogenate of myocardium of apex were taken

关 键 词：高血压 心血管系统 自由基 一氧化氮 

分 类 号：R544.1[医药卫生—心血管疾病]