替米沙坦对压力超负荷大鼠心肌内皮素-1表达和GATA DNA结合活性的影响  

Effects of telmisartan on endothelin-1 protein expression and GATA DNA binding activity in rats with left ventricular hypertrophy induced by pressure overload

作　　者：苟晓燕[1] 李法琦[2] 周希[3,4] 余江恒[5] 周平[2] 陈运贞[2] 

机构地区：[1]重庆市第一人民医院心内科,重庆400010 [2]重庆医科大学附属第一医院老年病科心血管病组 [3]重庆市急救医疗中心 [4]重庆市第四人民医院心内科 [5]自贡市第一人民医院心内科

出　　处：《中国老年学杂志》2010年第22期3315-3317,共3页Chinese Journal of Gerontology

摘　　要：目的研究压力超负荷心肌肥厚大鼠心肌组织(GATA)DNA结合活性和内皮素(ET)-1蛋白表达的变化及其意义,观察替米沙坦对压力超负荷心肌肥厚大鼠血流动力学参数〔收缩压(SBP)、舒张压(DBP)和平均压(MBP)〕、左室质量指数(LVM I)、心肌细胞横径(DC)、心肌组织GATA DNA结合活性和ET-1蛋白表达的影响。方法腹主动脉缩窄法建立压力超负荷大鼠心肌肥厚模型。健康SD大鼠24只,随机分为三组:假手术组(n=8);手术组(n=8);替米沙坦组(手术后第7天给替米沙坦3 mg.kg-1.d-1灌胃4 w,n=8)。测定大鼠SBP、DBP、MBP、LVM I及DC;免疫组化半定量检测心肌组织ET-1蛋白的表达,电泳迁移率变动分析检测ET-1与GATA的特异性结合及GATA DNA结合活性的变化。结果 ①与假手术组比较,手术组SBP、DBP、MBP、LVM I和DC均显著升高(P均<0.05);光镜下见心肌实质、间质结构改变;心肌组织ET-1蛋白表达和GATADNA结合活性均明显增加(P均<0.05);心肌组织ET-1蛋白表达与LVM I和DC均呈显著正相关(r=0.895,r=0.899,P均<0.01);②与手术组比较,替米沙坦组SBP、MBP、LVM I、DC、心肌组织ET-1蛋白表达和GATA DNA结合活性均明显降低(P均<0.05)。结论 (1)GATA DNA结合活性增加使ET-1蛋白表达增加与压力超负荷大鼠的心肌肥厚有关;(2)替米沙坦能够抑制压力超负荷大鼠的心肌肥厚,其机制可能与替米沙坦降低GATADNA结合活性从而下调ET-1蛋白表达有关。Objective To study the change and significance of endothelin-1（ET1） protein expression and GATA DNA binding activity in myocardium of rats with left ventricular hypertrophy induced by pressure overload and investigate the effects of telmisartan on hemodynamic parameters（systolic blood pressure（SBP）,diastolic blood pressure（DBP） and mean blood pressure（MBP））,left ventricular mass index（LVMI） and transverse diameter of myocardial cell（DC） as well as ET-1 protein expression and GATA DNA binding activity in myocardium of rats with left ventricular hypertrophy induced by pressure overload.Methods Experimental rats with left ventricular hypertrophy induced by pressure overload were established by partially banding abdominal aortic artery.24 healthy SD rats were randomly divided into three groups： sham-operated group（n=8）;operated group（n=8） and telmisartan group（telmisartan 3 mg·kg^-1·d^-1 per gavage,from 7th day to 4 weeks after operation,n=8）.Hemodynamic parameters,LVMI and DC were measured.ET-1 protein expression in myocardium was determined by immunohistochemistry assay.The specific combination of ET-1 with GATA and GATA DNA binding activity were analyzed with electrophoretic mobility shift assays（EMSA）.Results Compared with sham-operated group,SBP,DBP,MBP,LVMI,DC,ET-1 protein expression and GATA DNA binding activity were significantly increased（all P〈0.05）;and ET1 protein expression was correlated positively with LVMI and DC（r=0.895,r=0.899,all P〈0.01） in operated group.Compared with the operated group,SBP,MBP,LVMI,DC, ET-1 protein expression and GATA DNA binding activity were significantly reduced in telmisartan group（all P〈0.05）.Conclusions（1） The upregulation of ET-1 protein expression triggered by increase of GATA DNA binding activity is correlated with left ventricular hypertrophy of rats induced by pressure overload.（2） Telmisartan can prevent left ventricular hypertrophy of rats induced by pressure overload through downregulation ET-1

关 键 词：心肌肥厚 内皮素-1 GATA转录因子 替米沙坦 

分 类 号：R363[医药卫生—病理学]