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目的:研究缬沙坦、氨氯地平及螺内酯三种降压药物不同的联用方式对大鼠腹主动脉部分缩窄引起心肌肥厚的影响。方法:30只SD大鼠建立心肌肥厚模型后随机分为5组:假手术组,模型组,缬沙坦组,联合螺内酯组,联合氨氯地平、螺内酯组。术后给药,观察超声指标、计算心脏质量指数(HMI)及左心室质量指数(LVMI);应用逆转录多聚酶链反应(RT-PCR)检测心肌组织Ⅰ型和Ⅲ型胶原信使核糖核酸(mRNA)水平,苏木素伊红(HE)染色及masson染色方法测定心肌胶原沉积。结果:各用药组(缬沙坦组,联合螺内酯组,联合氨氯地平、螺内酯组)较模型组:大鼠室壁结构、心脏质量指数、心肌胶原沉积各项指标均降低,而射血分数值升高,差异均有统计学意义(P<0.05~0.01);其中联合氨氯地平、螺内酯组各指标较缬沙坦组、联合螺内酯组下降幅度最大。HE及masson染色结果显示联合氨氯地平、螺内酯组较缬沙坦组、联合螺内酯组大鼠心肌肥厚及胶原纤维沉积改善效果最佳。RT-PCR结果显示,心肌组织Ⅰ型和Ⅲ型胶原mRNA的相对表达量模型组较其他4组明显增高,差异均有统计学意义(P<0.05)。结论:缬沙坦、氨氯地平及螺内酯三药联用能有效逆转左心室肥厚,减少心肌纤维化及胶原沉积,效果优于缬沙坦单用及缬沙坦和螺内酯两药联用。
OBJECTIVE: To study the effects of different combinations of valsartan, amlodipine and spironolactone on cardiac hypertrophy induced by partial constriction of abdominal aorta in rats. Methods: Thirty SD rats were randomly divided into 5 groups: sham-operated group, model group, valsartan group, combined spironolactone group, amlodipine and spironolactone group. After operation, the indexes of ultrasound were observed and the cardiac mass index (HMI) and left ventricular mass index (LVMI) were calculated. The expression of type Ⅰ and type Ⅲ collagen messenger ribonucleic acid (mRNA) mRNAs in myocardium was detected by reverse transcription polymerase chain reaction ) Level, hematoxylin and eosin (HE) staining and masson staining. Results: Compared with the model group, the rats in the valsartan group, the combined spironolactone group, the amlodipine group and the spironolactone group showed that the indexes of the ventricular wall structure, the cardiac mass index and the myocardial collagen deposition decreased, while the ejection fraction (P <0.05 ~ 0.01). The indexes of combination of amlodipine and spironolactone had the largest decrease compared with those of valsartan and spironolactone. The results of HE and masson staining showed that the combination of amlodipine and spironolactone had the best improvement on myocardial hypertrophy and collagen deposition in the valsartan and spironolactone groups. The results of RT-PCR showed that the expression of type Ⅰ and type Ⅲ collagen mRNA in myocardial tissue in model group was significantly higher than the other 4 groups (P <0.05). Conclusion: Combination of valsartan, amlodipine and spironolactone can effectively reverse left ventricular hypertrophy and reduce myocardial fibrosis and collagen deposition. The combination of valsartan, amlodipine and spironolactone is superior to valsartan alone and valsartan combined with spironolactone.