犬心肌梗死后血管紧张素受体的异常分布及缬沙坦对其的调节作用  

Effects of valsartan on angiotensin II receptor distribution after myocardial infarction in dogs

作　　者：曲秀芬[1] 李晶洁[1] 喜杨[1] 沈景霞[1] 修春红[1] 岳乐[1] 王桂照[1] 黄永麟[1] 

机构地区：[1]哈尔滨医科大学附属第一医院心内科,150001

出　　处：《中华心血管病杂志》2009年第4期358-362,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30470687）;黑龙江省自然科学基金资助项目（D2007-42）

摘　　要：目的探讨心肌梗死（MI）后心脏局部不同部位血管紧张素受体的分布情况及其对局部心室功能的影响，评价缬沙坦对其的调节作用，进一步阐明缬沙坦对心脏的保护机制。方法将21只犬随机分为假手术组、MI组与缬沙坦组（MI后每天给予缬沙坦10mg／kg），后两组建立左心室前侧壁MI模型。术后4周应用组织多普勒超声检测梗死区近端心底部及远端心尖部梗死比邻的非梗死区各部位心室功能；应用免疫组织化学技术及定量逆转录-聚合酶链反应检测上述部位血管紧张素Ⅱ（AngⅡ）1型受体（AT1）和2型受体（AT2）蛋白及mRNA表达情况，假手术组在MI组对应部位取材。结果MI组心底及心尖部AT1受体蛋白和mRNA表达量均高于假手术组（P〈0．05），缬沙坦组AT1受体蛋白和mRNA表达量均低于MI组（P〈0．05），心尖部低得明显。MI组心底及心尖AT2受体蛋白及mRNA表达量高于假手术组（P〈0．05），缬沙坦组AT2受体蛋白和mRNA表达量均高于MI组（P〈0．05）。MI组心尖侧心肌收缩峰值速度（Sm）、舒张早期峰值速度（Em）和舒张晚期峰值速度（Am）较心底侧降低的比率[（心底侧-心尖侧）／心底侧]（分别为79．5％±3．3％，77．3％±5．3％，86．3％±2．5％）明显大于假手术组（分别为46．7％±8．5％，36．5％±5．2％，40．7％±7．8％，均P〈0．01）和缬沙坦组（分别为63．5％±5．8％，53．9％±6．6％，55．5±6．1％，均P〈0．01），缬沙坦组较MI组局部心肌收缩速度明显恢复。结论MI后压力负荷促使AT1、AT2受体蛋白及mRNA表达量增加，缬沙坦能够抑制AT1受体上调，促进AT2受体上调，对心脏起保护作用。Objective To investigate the effects of valsartan on expression of angiotensin Ⅱ receptors in different regions of heart after myocardial infarction （MI）. Methods Canines were divided into sham-operated control group （ n = 7 ）, infarction group （ n = 7 ） and Valsartan group （ 10 mg · kg^- 1 . day^- 1 for 4 weeks after MI operation, n = 7）. Four weeks after operation, Doppler tissue imaging （DTI） was used to evaluate regional ventricular function in the noninfarcted myocardium （apical and basal near to the infarction region）. The mRNA and protein expressions of angiotensin Ⅱ type 1 receptor （ AT1-R） and angiotensin Ⅱ type 2 receptor（AT2-R） on the corresponding regions were detected by competitive reversetranscriptase polymerase chain reaction technique and immunohistochemical technique respectively. Results The protein and mRNA expressions of ATI-R were significantly increased in both apical and basal regions near to the infarction in dogs with MI compared with those in control group （ P 〈 0. 05 ） which could be downregulated by valsartan （ P 〈 0.05 ）. AT2-R expressions were significantly upregulated in infarction group in both apical and basal regions compared with those in control group and valsartan further increased AT2-R expressions in both areas （ P 〈 0.05 ）. Myocardial peak systolic velocity （ Sm）, myocardial peak early diastolic velocity （Era） and myocardial peak late diastolic velocity （Am） at both apical and basal regions near to the infarction regions were significantly lower in MI group than those in the control group which could be significantly improved by valsartan. Conclusion Both mRNA and protein expressions of AT1 -R and AT2- R are upregulated in noninfarcted regions near MI, valsartan improved myocardial function via inhibiting AT1-R upregulation and enhancing AT2-R upregulation.

关 键 词：心肌梗死 血管紧张素受体 心室功能 降血脂药 

分 类 号：R686[医药卫生—骨科学]