醛固酮阻滞对心肌梗死大鼠非梗死区心肌组织胶原重塑的影响

Effects of aldosterone blockade on collegen remodeling in non-infarcted myocardium after myocardial infarction

目的研究醛固酮阻滞对心肌梗死大鼠非梗死区心肌组织胶原重塑的影响。方法将心肌梗死后24h存活大鼠随机分为2组:盐水组(22只,5ml/d),螺内酯组(23只,20mg/kg);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;组织学方法检测胶原纤维沉积;化学比色法测定胶原含量;免疫组化法观察胶原Ⅰ/Ⅲ比值;RT-PCR检测Ⅰ型胶原及Ⅲ型胶原mRNA的表达。结果①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,与假手术组相比差异有统计学意义(P<0.01)。与盐水组相比,螺内酯组心肌间质纤维沉积减轻,左室重量指数降低,差异有统计学意义(P<0.01);②与假手术组相比,心肌梗死组非梗死区的胶原含量增加,胶原Ⅰ/Ⅲ比值升高,Ⅰ型、Ⅲ型胶原mRNA水平增加,差异具有统计学意义(P<0.05,P<0.01)。与盐水组相比,螺内酯组非梗死区胶原含量、非梗死区胶原Ⅰ/Ⅲ比值、Ⅰ型及Ⅲ型胶原mRNA水平均降低,差异具有统计学意义(P<0.05,P<0.01);③与假手术组相比,所有心肌梗死大鼠6周后左室收缩压(LVSP)和左心室内压最大上升和下降速率(±dp/dtmax)均显著下降,LVEDP显著上升,差异有统计学意义(P<0.01);与盐水组相比,螺内酯组大鼠心功能显著改善,差异有统计学意义(P<0.01)。结论心肌梗死后大鼠非梗死区心肌组织出现胶原重构;醛固酮阻滞能改善心肌的纤维化,改善心脏功能。

Objective To investigate the effects of aldosterone blockade on coliegen remodeling in myocardial infarcted（MI） rats. Methods 45 rats that survived 24 hours after ligation of left anterior descending coronary artery were randomly divided into two groups ：MI-saline group（ n = 22,5 ml/d）and MI-splronolacton（ n =23,20 mg/kg · d）. Sham operation group（ n = 15 ）was selected as non-infarction control. 6 weeks after drug therapy by gastric gavage, hemodynamics and left ventricular function were measured with catheterization, interstitial fibrosis infiltration was evaluated with histological methods, collagen was measured by colorimetric method,type Ⅰ and type Ⅲ collagen were analyzed by immunohistochemical method, mRNA expression of type Ⅰ and type Ⅲ collagen was measured by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results （1） Compared with the sham operation group, rats in MI group showed marked interstitial fibrosis infiltration in noninfarction area, higher ventricular weight/body weight ratio, （ P 〈 0. 01, respectively）. （2）Compared with the sham operation group, the synthesis of collagen was increased in non-infarcted myocardium. The ratio of type Ⅰ/Ⅲ collagen and the mRNA expression of type Ⅰ and type Ⅲ collagen were also increased（P 〈 0. 05, P 〈 0. 01 ）. Spironolacton significantly decreased the synthesis of collagen, the ratio of type Ⅰ/Ⅲ collagen and the mRNA expression of type Ⅰ and type Ⅲ collagen in non-infarcted myocardium at 6 weeks after infarction（ P 〈0. 05 ,P 〈 0.01 ）. （3）All infarcted rats developed significant systolic and diastolic dysfunction, as indicated by decreased LVSP and ＋ dp/dtmax, as well as increased LVEDP（ P 〈 0. 01, respectively）. Aldosterone blockade significantly prevented cardiac fibrosis and systolic and diastolic dysfunction （P 〈0.01, respectively）. Conclusion Aldoste- lone blockade prevents cardiac collagen remodeling in non-infarcted myocardium after MI.