小剂量贝那普利联合螺内酯对自发性高血压大鼠心肌纤维化的干预作用及超声背向散射积分评价

Study of the Myocardial Interstitial Fibrosis and Effect of Small Dose of Benazepril with Spironolactone on Spontaneously Hypertensive Rats by Integrated Backscatter Technique

目的观察小剂量贝那普利联合螺内酯对自发性高血压大鼠(SHR)左室心肌纤维化的影响,并应用超声背向散射积分(IBS)进行评价。方法21只雄性SHR随机分成模型对照组(SHR组)、贝那普利干预组[SHR-B组,贝那普利10mg/(kg·d)灌胃]及小剂量贝那普利联合螺内酯干预组[SHR-BS组,贝那普利5mg/(kg.d)+螺内酯10mg/(kg·d)灌胃],另外选择同周龄雄性Wistar大鼠设为正常对照组(WKY组),SHR组及WKY组蒸馏水灌胃2mL/d。12周后超声测量IBS参数[峰-峰强度(PPI);平均图像强度(AII)];对心肌组织进行羟脯氨酸含量(HPC)测定,Masson染色计算胶原容积分数(CVF)、血管周围胶原面积(PVCA)、冠状小动脉管壁厚/管外径比值(T/D),嗜银染色计算嗜银纤维容积分数(APFVF),对结缔组织生长因子(CTGF)蛋白表达的半定量分析进行免疫组织化学染色。结果与WKY组比较,SHR组的超声AII%明显增高,PPI减低,SHR组的纤维化指标(HPC、CVF、PVCA、T/D、APFVF、CTGF的表达)增高。干预后,与SHR组比较AII%减低,PPI增高,纤维化指标减轻,但未达WKY组水平。SHR-B与SHR-BS两干预组间各参数比较无显著性差异。AII%与纤维化指标呈正相关。结论SHR的心肌纤维化,伴有心肌CTGF高表达。SHR-BS组与SHR-B组比较,在抑制CTGF的表达、减轻心肌间质纤维化方面无明显差异,但价效比更优越。

Objective To investigate the effect of small dose of benazepril with spironolactone on the left ventricular myocardial fibrosis accessed by integrated backscatter（IBS）technique in spontaneously hypertensive rats（SHR）.MethodsTwenty-one male SHRs were divided equally into three groups： benazepril [SHR-B, given benazepril 10 mg/（kg·d）], low dose of benazepril with spironolactone[SHR-BS, 5 mg/（kg·d） benazepril with 10 mg/（kg·d） spironolactone] group and control （SHR） group.WKYs served as the normal control（WKY）. Drugs were administered by gavage.WKY and SHR control received 2 mL distilled water.After 12 weeks, AII%, PPI were determined by ultrasonography.The myocardial hydroxyproline concentration （HPC） were determined, Masson staining and Argyrophilic staining were used to access collagen volume fraction （CVF）, perivascular collagen area（PVCA）,ratio of small coronary artery wall thickness to external diameter （T/D） and argyrophilic fibers volume fraction（APFVF） in heart tissue.The expression of CTGF was evaluated by qualitative and semiquantitative immunohistochemical staining.ResultsThe AII% and fibrosis index （including HPC, CVF,PVCA,T/D, APFVF, CTGF） were significantly higher and PPI was lower in SHR group than those in WKY group.The AII% and fibrosis index were decreased, and PPI was increased both in SHR-B and SHR-BS groups after treatment, but it did not return to baseline levels of WKY group.There was no difference between SHR-B group and SHR-BS group after treatment（P〉0.05）.The correlation between AII% and fibrosis index was significant.ConclusionsThe myocardial interstitial fibrosis in SHR was accompanied by the upregulation of CTGF in myocardium of rat.There were no difference of CTGF expression and left ventricular myocardial interstitial fibrosis between the groups of small dose of benazepril with spironolactone and the group of benazepril, small dose group has a better cost-effective ratio.