血管紧张素Ⅱ及醛固酮阻滞剂对心肌梗死大鼠骨桥蛋白表达的影响  

Blockades of Angiotensin Ⅱ and Aldosterone Inhibit Osteopontin Expression in Non-infarcted Myocardium after Myocardial Infarction

作　　者：张玉玲[1] 周淑娴[1] 雷娟[1] 张静敏[1] 

机构地区：[1]中山大学附属第二医院心血管内科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2007年第6期662-665,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金资助项目(4009434)

摘　　要：【目的】研究血管紧张素Ⅱ及醛固酮阻滞对心肌梗死大鼠非梗死区心肌组织骨桥蛋白(OPN)表达的影响。【方法】将心肌梗死后24h存活大鼠随机分为3组:盐水组(15只,5mL/d),培哚普利组(18只,2mg/kg·d)和螺内酯组(17只,20mg/kg)。灌胃给药;另设假手术组(15只)作对照。分别于心肌梗死后6周:导管法测定左室有创血流动力学;组织学方法检测非梗死区胶原纤维沉积和心肌细胞横径;Western blot检测非梗死区心肌组织OPN表达。【结果】①假手术组大鼠心肌组织Western blot未检测到OPN表达,心肌梗死大鼠6周后非梗死区心肌组织有大量OPN表达,培哚普利及螺内酯治疗均能显著抑制该蛋白的上调,差别均有统计学意义(P均<0.01)。②与假手术组相比,所有心肌梗死大鼠均出现显著的心肌间质纤维沉积,左室重量指数增大,非梗死区心肌细胞横径增加,差别均有统计学意义(P均<0.01)。与盐水组相比,培哚普利及螺内酯组心肌间质纤维沉积减轻,左室重量指数及非梗死区心肌细胞横径降低,差别均有统计学意义(P均<0.01)。③与假手术组相比,所有心肌梗死大鼠6周后左室内收缩压(LVSP)和±dp/dtmax均显著下降,左室舒张末期压(LVEDP)显著上升,差别均有统计学意义(P均<0.01);与盐水组相比,培哚普利与螺内酯组大鼠心功能显著改善,差别均有统计学意义(P均<0.01)。【结论】心肌梗死后大鼠非梗死区心肌组织出现大量OPN表达及显著的心室重构;血管紧张素Ⅱ及醛固酮阻滞均能显著抑制心肌梗死大鼠OPN的表达,并能改善心肌的纤维化,改善心脏功能。[Objective] To elucidate the effects of blockades of angiotensin Ⅱ and aldosterone on cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted （MI） rats. [Methods] After ligating left anterior descending coronary artery, 50 rats that survived 24 h were randomly divided into three groups： MI-saline group （n=15, 5 mL/d）, MI-perindopril group （n=18, 2 mg/kg.d） and MI-spironolactone （n=17, 20 mg/kg.d）. Sham operated group （n=15） was selected as non-infarcted control. At 6 weeks after drug therapy by gastric gavag, hemodynamics and left ventricular function were measured with catheterization. Interstitial fibrosis infiltration and cardiomyocyte diameter were evaluated with histological methods. Myocardium osteopontin protein expression level in non-infarcted myocardium was detected with Western blot analysis. [Results] （1）No osteopontin protein was detected in myocardium of sham-operation rats. At 6 weeks after MI, high level osteopontin protein expression was detected in non-infarcted myocardium. Blockades of angiotensin Ⅱ and aldosterone significantly suppressed increased osteopontin protein expression in non-infarcted myocardium at 6 weeks （P〈 0.01, respectively）. （2）Compared with the sham operated group, the rats in MI group showed marked interstitial fibrosis infiltration in non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter （P〈 0.01, respectively）, and developed significant systolic and diastolic dysfunction, as was indicated by decreased left ventricular systolic pressure（LVSP） and the maximum rising and dropping rates of left ventricular pressure （±dp/dmax）, as well as increased left ventricular end-diastolic pressure （LVEDP） （P〈 0.01, respectively）. Angiotensin and aldosterone blockades significantly prevented cardiac fibrosis and systolic and diastolic dysfunction （P〈 0.01, respectively）. [Conclusions] Angiotensin Ⅱ and aldosterone blockades

关 键 词：骨桥蛋白 心肌梗死 血管紧张素-醛固酮阻滞剂 

分 类 号：R542.220[医药卫生—心血管疾病]