安体舒通改善自发性高血压大鼠心肌纤维化  

Spironolactone improves myocardial fibrosis in spontaneously hypertensive rats

作　　者：许明[1] 杨汉东[1] 闵新文[1] 李东峰[1] 

机构地区：[1]郧阳医学院附属东风医院心内科,湖北十堰442008

出　　处：《中国病理生理杂志》2008年第7期1281-1285,共5页Chinese Journal of Pathophysiology

基　　金：湖北省十堰市科技局资助项目(No.2005ZD050)

摘　　要：目的:观察安体舒通对自发性高血压大鼠(spontaneously hypertensive rats,SHR)心肌纤维化的影响及可能机制。方法:将16只14周龄雄性SHR随机分为安体舒通组和对照组,每组8只,分别以安体舒通30mg.kg-1.d-1及等量生理盐水灌胃12周,同时取8只同龄雄性SD大鼠作为正常对照组,用免疫组化的方法对结缔组织生长因子(connective tissue growth factor,CTGF)、转化生长因子β1(transforming growth factors beta-1,TGFβ1)、胶原Ⅰ和Ⅲ(collagenⅠandⅢ)在大鼠左室心肌的分布及表达进行半定量分析;用RT-PCR的方法检测TGFβ1、CTGFmRNA在心肌表达水平;用Masson染色法观察左室心肌胶原形态,图像分析测量胶原容积分数(colla-gen volume fraction,CVF);用碱水解法测定左室心肌羟脯氨酸(hydroxyproline,Hypro)含量。结果:(1)SHR对照组左室重量指数(left ventricular index,LVI)、CVF、Hypro、collagenⅠ和Ⅲ、CTGF、TGFβ1蛋白及mRNA表达明显高于SD大鼠组(P<0.01);相对于SHR对照组,安体舒通组则显著降低(P<0.05);(2)相关分析表明:CTGF与TGFβ1、CVF、Hypro和LVI呈高度正相关(P<0.01)。结论:安体舒通能明显改善SHR心肌纤维化,其作用可能是通过阻断盐皮质激素受体和抑制CTGF的表达而实现的。AIM： To observe the effect of spironolactone on myocardial fibrosis of spontaneously hypertensive rats （SHR）. METHODS： Sixteen fourteen- weekold male SHRs were randomly assigned to spironolactone and SHR group equivalently （ n = 8）. Rats in each group were given 30 mg ·kg^-1 · d^-1 spironolactone and equal sodium chloride respectively for 12 weeks by gavage. Eight fourteen - week - old male SD rats were as control group. Connective tissue growth factor （ CTGF）, transforming growth factors beta - 1 （ TGFβ1）, collagen Ⅰ and Ⅲ were measured by qualitative and semiquantitative immunohistochemical staining and semiquantitative reverse transcription polymerase chain reaction. Masson staining was used to determine total collagen in left ventriculum. Alkaline hydrolysis method was used to detect the concentration of hydroxyproline （Hypro） in the myocardium of left ventricle. RESULTS： Left ventricular index （LVI）, collagen volume fraction （CVF） , Hypro and the expression of TGFβ1 , CTGF, collagen Ⅰ and Ⅲ in SHR group were significantly higher than those in SD group （P 〈 0. 01 ）. Compared with the SHR group, these indexes in spironolactone treatment group decreased obviously （ P 〈 0.05 ）. CONCLUSION： Spironolactone significantly improves myocardial fibrosis of SHR by blocking mineralocorticoid receptor and suppressing the expression of CTGF.

关 键 词：安体舒通 自发性高血压大鼠 结缔组织生长因子 心室重构 心肌纤维化 

分 类 号：R363[医药卫生—病理学]