正常盐饮食状态下醛固酮增多对心肌纤维化的作用  

Effect of Aldosterone on the Blood Pressure,Cardiac Structure and Function in the Absence of High-salt Intake in Rats

作　　者：李静宜[1] 张少玲[1] 黎锋[1] 严励[1] 李焱[1] 程桦[1] 

机构地区：[1]中山大学附属第二医院内分泌科,广东广州510120

出　　处：《中华高血压杂志》2009年第7期593-598,共6页Chinese Journal of Hypertension

基　　金："十五"国家科技攻关重大计划(2004BA720A29)

摘　　要：背景既往研究认为醛固酮增多时,要在高盐或单侧肾切除情况下才能引起心肌纤维化。目的观察在正常盐饮食情况下,醛固酮增多对Sprague-Dawley(SD)大鼠血压和左心室心肌的影响,并探讨其相关机制。方法在正常盐饮食(氯化钠浓度0.4%)的情况下,皮下给予大鼠醛固酮(0.75μg/h)8周,建立醛固酮增多大鼠模型,8只年龄、体质量匹配的SD大鼠为对照组。用尾动脉方法监测血压变化,观察血浆和24h尿液钠、钾离子水平,心脏超声检查左心室变化,左心室心肌组织Masson染色观察胶原,心肌组织免疫组化方法观察3硝基酪氨酸的表达,并检测血清8异前列烷浓度和血清醛固酮水平及血浆肾素活性。结果与正常大鼠比较,在正常盐饮食的情况下给予醛固酮干预组(干预组)大鼠血清醛固酮浓度增加[对照组(623.1±80.1)比干预组(1664.9±72.2)ng/L,P<0.01],血浆肾素活性降低[对照组(7.22±0.07)比干预组(4.17±0.55)ng/(mL.h),P<0.01],血压显著升高[对照组(127±3)比干预组(162±4)mmHg,P<0.01],左心室心肌组织胶原容积分数明显增加[对照组(1.44±0.31)%比干预组(3.43±0.23)%,P<0.01],左心室质量指数增加[对照组(2.1±0.1)比干预组(2.4±0.2)mg/g,P<0.05],心脏舒张功能降低。心肌组织3硝基酪氨酸表达上调,血清8异前列烷浓度升高[对照组(327.0±79.7)比干预组(753.1±85.9)ng/L,P<0.05]。结论在不依赖盐负荷的情况下,单纯醛固酮增多可引起机体氧化应激反应增强,导致血压升高,心肌组织肥厚和心脏舒张功能降低。Background Previous reports indicated aldosterone-mediated cardiac fibrosis required the combination of a moderately high salt intake. Objective To test the hypothesis that the effect of excess aldosterone in the absence of high salt diet on the blood pressure and myoeardium fibrosis in Sprague-Dawley （SD） rats and to investigate the potential mechanism. Methods Rats were infused subcutaneously with aldosterone （0.75 μg/h） by minipump for 8 weeks with a normal salt diet （n= 8） and 8 age and weight matched SD rats as control. SBP was measured by the tail-cuff method. Food intake arid urine volume were recorded in metabolic cages. The plasma and urine Na^＋ and K^＋ were measured. Transthoracic echocardiographic studies were performed at the eighth week. 3-nitrotyrosine expression of myocardium was analyzed by immunohistochemistry. The serum 8-isoprostane levels, serum aldosterone concentration and plasma renin activity were measured. Results Aldosterone increased left ventricular mass index [control （2.1±0.1） vs treated （2.4±0.2）mg/g, P〈0.05] and decreased E/A [control （ 1.74± 0. 18 ） vs treated （0.94±0. 19 ） ] with significantly elevated blood pressure [control （ 127 ± 3 ） vs treated （162±4）mmHg, P〈0.01] in the rats with aldosterone combined normal-salt diet. Aldosterone-infused rats had higher myocardial collagen volume fraction [ treated （ 3.43 ± 0.23 ） % vs control （ 1. 44 ± 0. 31 ） %, P〈0.01], higher 3-nitrotyrosine expression of myocardium and serum levels of 8-isoprostane. Conclusion Aldosterone might lead to hypertension, left ventricular hypertrophy and fibrosis and the decreased diastolic function without combination of high salt intake.

关 键 词：醛固酮 胶原沉积 氧化应激 

分 类 号：R541[医药卫生—心血管疾病]