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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 effect of aldosterone block on collagen remodeling in non-infarcted myocardium in rats with myocardial infarction. Methods 24 h after myocardial infarction were randomly divided into 2 groups: saline group (22, 5ml / d), spironolactone group (23, 20mg / kg); The left ventricular invasive hemodynamics were measured by catheterization method at 6 weeks after myocardial infarction. The deposition of collagen fibers was detected by histological method. The collagen content was determined by chemical colorimetry. The ratio of collagen Ⅰ / Ⅲ was observed by immunohistochemistry. The expression of type Ⅰ collagen and type Ⅲ collagen mRNA was detected. Results ① All myocardial infarction rats showed significant myocardial interstitial fibrosis, left ventricular mass index increased, compared with the sham operation group, the difference was statistically significant (P <0.01). Compared with the saline group, the myocardial interstitial fibrosis of the spironolactone group decreased and the left ventricular mass index decreased, with statistical significance (P <0.01). ②Compared with the sham operation group, the collagen content in non-infarct area increased (P <0.05, P <0.01). Collagen Ⅰ / Ⅲ ratio increased, and type Ⅰ and type Ⅲ collagen mRNA levels increased. Compared with the saline group, the collagen content in the non-infarct zone, collagen Ⅰ / Ⅲ ratio, collagen type Ⅰ and Ⅲ mRNA in spironolactone group were significantly decreased (P <0.05, P <0.01); ③ Compared with the sham-operation group, LVSP and ± dp / dtmax decreased significantly and LVEDP increased significantly after 6 weeks in all myocardial infarction rats, the difference was statistically significant (P <0.01). Compared with saline group, the cardiac function of rats in spironolactone group was significantly improved, with statistical significance (P <0.01). Conclusion Myocardial infarction in non-infarcted area of myocardial collagen remodeling; aldosterone block can improve myocardial fibrosis and improve cardiac function.