贝那普利和氯沙坦联合治疗对自发性高血压大鼠左室重构的影响  

Combination Effects of Benazepril and Losartan on the Reversal Left Ventricular Remodeling in Spontaneously Hypertensive Rat

作　　者：张子强[1] 朱竹先[2] 刘雪平[3] 高顺宗[3] 解建[1] 姜志明[1] 

机构地区：[1]山东省千佛山医院ICU,济南250014 [2]山东省千佛山医院血液净化中心,济南250014 [3]山东省立医院老年病科,济南250021

出　　处：《高血压杂志》2006年第3期196-200,共5页Chinese Journal of Hypertension

基　　金：中央保健专项基金(鲁A032)

摘　　要：目的探讨贝那普利和氯沙坦联合应用对自发性高血压大鼠(SHR)左心室重构的作用。方法48只55周龄SHR随机分组(n=12):空白对照组(SHRC)、贝那普利组(SHRB:10mg/kg·d)、氯沙坦组(SHRL:30mg/kg·d)、合用组(SHRB+L:贝那普利10mg/kg·d+氯沙坦15mg/kg·d),另设WKY大鼠为对照组,检测尾动脉压(SBP)。12周后:(1)放射免疫法检测血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)、醛固酮(Ald)水平,化学法检测血浆一氧化氮(NO)水平;(2)免疫组化法检测心肌Ⅰ、Ⅲ型胶原纤维表达;(3)病理及超微结构检测。结果与SHR对照组比较,各药物组尾动脉压显著下降(P<0.01),但用药组间无显著差异(P>0.05);SHR各组间血浆PRA无显著性差异(P>0.05)。SHR对照组血浆AngⅡ低于WKY对照组(P<0.05～0.01),贝那普利组显著降低和氯沙坦组显著升高血浆AngⅡ水平,合用组介于两组之间。与贝那普利组[Ald:(393.9±17.6)pg/mL、NO:(15.2±2.1)μmol/L]、氯沙坦组[Ald:(332.0±17.8)pg/mL、NO:(12.3±1.8)μmol/L]比较,合用组[Ald:(302.4±15.5)pg/mL、NO:(16.5±2.4)μmol/L]更显著的降低血浆Ald和升高NO水平(P<0.01);与贝那普利组(Ⅰ型胶原:6.09±1.12%、Ⅲ型胶原:9.0%±1.2%)、氯沙坦组(Ⅰ型胶原:4.3%±0.7%、Ⅲ型胶原:8.0%±1.3%)比较,合用组(Ⅰ型胶原:2.8%±0.7%、Ⅲ型胶原:6.5%±1.0%)更显著的降低心肌Ⅰ、Ⅲ型胶原纤维的表达(P<0.01);组织病理及电镜显示,合用组更显著的改善SHR左心室重构。结论贝那普利和氯沙坦均能有效的改善高血压左室重构,二者合用时更为明显。Objective To investigate the combinaed effects of Benazepril and losartan in reversal of left ventricular remodeling in SHR. Methods Fourty-eight SHR and 12 age matched WKY were divided into 5 groups randomly （ n = 12 ） ： （ 1 ） WKY-control group ; （ 2 ） SHR-control group ; （ 3 ） SHR-Benazepril group（ 10 mg/kg · d） ; （ 4 ） SHR-losartan group （ 30 mg/kg · d） ; （ 5 ） SHR-Benazepril （ 10 mg/kg · d ） ＋ losartan group （15 mg/kg · d）. After 12 weeks of treatment, serum angiotensin（Ang） Ⅰ , Ang Ⅱ, aldosterone（Ald）, and NO were measured. Myocardial pathologic and ultrastructural changes were determined. Levels of left ventricular Ⅰ and Ⅲ typed collegen were assessed by immunohistochemical methods. Results SBP of each treatment group was lower than that in SHR-control group significantly（ P〈 0. 01） , with no significant difference among them （P〉0.05）. PRA was not significant difference（ P〉 0.05）among the SHR groups. Combined treatment decreased the level of Ald, NO and the myocardium expression of Ⅰ , Ⅲ typed collagen than that by single benazepril and losartan. Meanwhile, pathological and ultrastructure observation demonstrated that the combination group reversed LVPI more effectively.Conclusion therapy ameliorate left ventricular remodelling, the effect of combined benazepril and losartan on the reversal of left ventricular hypertrophy was more pronounced than that by single therapy.

关 键 词：贝那普利 氯沙坦 联合应用 高血压 左心室重构 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]