坎沙曲联合缬沙坦与奥帕曲拉均减轻大鼠心肌肥厚

基础医学与临床 ›› 2012, Vol. 32 ›› Issue (8): 921-925.

坎沙曲联合缬沙坦与奥帕曲拉均减轻大鼠心肌肥厚

郑亚萍,王兴红

漯河医学高等专科学校

收稿日期:2011-12-29 修回日期:2012-05-05 出版日期:2012-08-05 发布日期:2012-07-17
通讯作者: 郑亚萍 E-mail:zhengya85@sohu.com.cn

Candoxatril combined losartan and omapatrilat decrease myocardial hypertrophy in rats

Received:2011-12-29 Revised:2012-05-05 Online:2012-08-05 Published:2012-07-17

摘要/Abstract

摘要： 目的比较坎沙曲联合缬沙坦与奥帕曲拉(OMA) 对大鼠心肌肥厚的保护作用。方法注射1mg/kg异丙肾上腺素(ISO)制备大鼠心肌肥厚模型，随机分为对照组、心肌肥厚组、坎沙曲组、缬沙坦组、OMA组与坎沙曲+缬沙坦（半量及全量）组，每组n =8，染色后测定心肌细胞横截面积、心肌间质胶原容积分数及血管周围胶原面积；免疫组化学检测心肌组织p-PI3K和p-Akt表达；放免法测定血浆血管紧张素Ⅱ(AngⅡ)、心房利钠肽（ANP）、缓激肽（BK）水平。结果 1)坎沙曲+缬沙坦（全量）及OMA组可均可降低心肌肥厚组大鼠心脏重量指数（分别为3.64±0.30、3.62±0.28和4.32±0.58）、心肌细胞横截面积、心肌间质胶原容积分数及血管周围胶原面积的明显上升 (均P < 0.01)，两组间无明显差异。2)与心肌肥厚组相比,坎沙曲+缬沙坦（全量）及OMA组均可降低血浆AngⅡ含量〔分别为（741±89）ng/L、（682±66）ng/L和（479±62）ng/L〕，并显著上调ANP〔分别为（117±33）μg/L、（298±91）μg/L和（288±95）μg/L〕及BK〔分别为（124±12）ng/L、(232±21) ng/L和(309±24）ng/L〕水平(均P < 0.01)，但坎沙曲+缬沙坦（全量）较OMA组BK的上调幅度低。3)坎沙曲+缬沙坦（全量）与OMA均下调心肌肥厚组心肌组织p-PI3K和p-Akt蛋白表达，且两者间无明显差异。结论坎沙曲联合缬沙坦与OMA均可减轻大鼠心肌肥厚, 但对血浆激素水平的影响有差异。

关键词: 心肌肥厚, 坎沙曲, 奥帕曲拉, 缬沙坦, 缓激肽

Abstract: Objective To compare the protective effect of candoxatril combined losartan on rat myocardial hypertrophy with omapatrilat (OMA) .Methods 1mg/kg isoproterenol (ISO) was given to induce myocardial hypertrophy in Sprague-Dawley (SD) rats. Rats were randomly divided into 7 groups: control, myocardial hypertrophy, candoxatril, losartan, OMA, candoxatril + losartan(full dose and half-value dose) （all n=8）. The myocardial hypertrophy index was expressed as heart weight /body weight (HW/BW),cross-sectional area (CSA), myocardial interstitial collagen volume fraction (CVF) and perivascular collagen area (PVCA); The content of plasma angiotensinⅡ(AngⅡ), atrial natriuretic peptide (ANP)and bradykinin (BK)were measured by colorimetry and radioimmunoassay;The expression of p-PI3K and p-Akt protein were detected by immunohistochemistry staining. Results 1) compared to control, ISO significantly increased heart weight index（3.64±0.30, 3.62±0.28, 4.32±0.58 respectively）, CSA, CVF, PVCA (P < 0.01); candoxatril + losartan(full dose) and OMA can decreased the effect of ISO (P < 0.01) .2)ISO increased AngⅡcontent〔（741±89）ng/L,（682±66）ng/L and（479±62）ng/L respectively〕significantly and the ANP and BK level mildly compared to control. Compared to myocardial hypertrophy control group, candoxatril + losartan (full dose)and OMA both decreased plasma AngⅡ content and increased the ANP〔（117±33）μg/L,（298±91）μg/L,（288±95）μg/L respectively〕and BK〔（124±12）ng/L,(232±21) ng/L and (309±24）ng/L respectively〕level significantly (P < 0.01), but candoxatril + losartan make less BK level increase than OMA (P < 0.05).3) OMA down-regulated the expression of p-PI3K, p-Akt protein which is not better than candoxatril + losartan(full dose). Conclusion candoxatril combined losartan and OMA decrease myocardial hypertrophy in rats. There were differences in the plasma hormone level.

Key words: myocardial hypertrophy, Candoxatril, omapatrilat, losartan, bradykinin

中图分类号:

郑亚萍王兴红. 坎沙曲联合缬沙坦与奥帕曲拉均减轻大鼠心肌肥厚[J]. 基础医学与临床, 2012, 32(8): 921-925.

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