螺内酯对原发性高血压大鼠左心室功能的影响

Effects of spironolactone on left ventricular function in spontaneously hypertensive rats

目的用超声评价螺内酯对原发性高血压(高血压)大鼠(SHR)心肌组织胶原含量和心功能的影响。方法20只雄性高血压大鼠随机分为螺内酯组(n=10)和安慰剂组(n=10),另设WKY组(n=7)。螺内酯组螺内酯用双蒸水溶解后以20 mg.kg-1.d-1灌胃;安慰剂组和WKY组用等容积双蒸水灌胃,连续16周。超声心动图观察大鼠左心房内径,室间隔和后壁厚度,射血分数,背向散射积分(IBS);背向散射积分周期变化(PPI)。取心肌标本,称取左心室重量,计算左心室质量指数,制备心肌组织石蜡切片,天狼猩红饱和苦味酸染色,观察心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果与WKY组比较,安慰剂组大鼠心肌肥厚指标:左心室质量指数室,室间隔及左心室后壁厚度增加;心脏功能指标:左心房内径、射血分数增大,E/A比值减少;纤维化指标:胶原容积分数、血管周围胶原面积增加,声学密度指标背向散射积分升高,背向散射积分周期变化降低,差异有统计学意义(P<0.05)。治疗16周,与安慰剂组比较,螺内酯组上述指标均有改善,差异有统计学意义(P<0.05)。结论高血压大鼠左心室胶原沉积、心肌肥厚、舒张功能减退,收缩功能受损。螺内酯治疗能减少高血压大鼠局部胶原沉积,改善左心室功能。

Objectives To explore effects of spironolactone on myocardial collagen content and heart function in spontaneously hypertensive rats （SHR）. Methods Twenty male SHRs were randomly assigned into spironolactone group （n=10） and placebo group （n=10）, sex-age matched Wistar Kyoto rats （WKY group,n=7） were also designed. In spironolactone group, spironolactone was dissolved in distilled water and rats were given spironolactone 20 mg· kg-1. d-1 by intragastric administration. Meanwhile, rats in placebo group and WKY group were given the same quantative distilled water by intragastric administration. Left atrial diameter, interventricular septal thickness, posterior wall thickness, E/A ratio, ejection fraction, integrated backscatter （IBS）, peak to peak intensity （PPI） were examined by echocardiography for 16 weeks. Sirius red staining of myocardial tissue was used to evaluate collagen volume fraction （CVF） and perivascular collagen area （PVCA）. The heart and left ventricle were weighted to calculate left ventricular mass index （LVMI）. Results Left atrial diameter, interventricular septal thickness, posterior wall thickness, IBS, CVF and PVCA increased, while PPI and E/A ratio decreased significantly in placebo group when compared with WKY group （P〈0.05）. Compared with placebo group, after the treatment of 16 weeks, the above indexes of heart function and myocardial hypertrophy obviously improved in spironolactone group （P〈0.05）. Conclusions Left ventricular hypertrophy, collagen deposition, diastolic dysfunction and impaired contractile function are found in SHRs. The treatment of spironolactone can decrease collagen deposition and improve the function of left ventricle in hypertensive rats.