益心泰有效组分干预慢性心力衰竭心气虚兼血瘀水停证兔的疗效及作用机制研究

Therapeutic effect and mechanism of the effective componets of Yixintai in chronic heart failure rabbits with heart-qi deficiency complicated blood stasis and edema syndrome

目的:研究评价益心泰有效组分对慢性心力衰竭心气虚兼血瘀水停证兔的疗效及作用机制。方法:120只新西兰兔随机抽取20只作为正常对照组,剩余100只采用阿霉素耳缘静脉注射配合丙基硫氧嘧啶灌胃造模。将造模成功的兔随机分为模型组、益心泰有效组分低、中、高剂量组和氯沙坦钾组。各组相应药物灌胃给药28 d后,采用ELISA法检测血清氨基末端B型利钠肽(NT-pro BNP)水平,超声心动图检测左心室射血分数(LVEF)水平,血液流变仪检测全血高切黏度、全血低切黏度、血浆黏度,观察各组兔左心室重量指数及心、肝、肾脏组织病理形态,采用酶学比色法检测心肌组织钙调神经磷酸酶(CaN)活性,Western Blot法检测心肌活化T细胞核因子3磷酸化水平(p-NFAT3/NFAT3比值)及GATA结合蛋白4(GATA4)蛋白表达情况。结果:与正常对照组比较,模型组血清NT-pro BNP水平显著上升(P<0.01),LVEF显著下降(P<0.01),全血高切黏度、全血低切黏度、血浆黏度显著上升(P<0.01),左心室重量指数显著升高(P<0.01),心肌组织CaN活性显著增强(P<0.01),p-NFAT3/NFAT3比值显著下降(P<0.01),GATA4蛋白表达显著升高(P<0.01)。与模型组比较,ECYXT各剂量组及氯沙坦钾组血清NT-pro BNP水平显著降低(P<0.01),LVEF显著升高(P<0.01),全血高切黏度、全血低切黏度、血浆黏度显著降低(P<0.01),左心室重量指数显著降低(P<0.01),心肌组织CaN活性显著降低(P<0.01),p-NFAT3/NFAT3显著升高(P<0.01),GATA4蛋白表达显著降低(P<0.01)。结论:益心泰有效组分能抑制慢性心力衰竭心气虚兼血瘀水停证兔Ca N-NFAT3-GATA4信号通路,改善心室重构,提高心功能。

Objective:To study and evaluate the curative effect and mechanism of the effective componets of Yixintai(ECYXT)in intervening chronic heart failure(CHF)rabbits with heart-qi deficiency complicated blood stasis and edema syndrome.Methods:Twenty of 120 New Zealand rabbits were randomly selected as normal control group,and the remaining 100 rabbits were used to establish model by intravenous injection of adriamycin and intragastric administration of propylthiouracil The rabbits successfully modeled were randomly divided into model group,low dose group of ECYXT,medium dose group of ECYXT,high dose group of ECYXT and losartan potassium group.After twenty-eight days administration by corresponding drugs in each group,ELISA was used to detect the level of N-terminal B-type natriuretic peptide(NT-pro BNP)in serum,the left ventricular ejection fraction(LVEF)was detected by echocardiography,whole blood high shear viscosity,whole blood low shear viscosity,and plasma viscosity were detected by blood rheometer,the left ventricular mass index and pathological structure of myocardium,liver and kidney were observed and compared,the enzymatic colorimetry was used to detect the activity of CaN in myocardial tissue,the western blot were used to detected the p-NFAT3/NFAT3 radio and the expression of GATA4 protein in myocardial tissue.Results:Compared with normal control group,the level of NT-pro BNP in serum was increased in the model group(P<0.01),the LVEF was decreased(P<0.01),the whole blood high shear viscosity,whole blood low shear viscosity,and plasma viscosity were increased(P<0.01),the left ventricular mass index was increased(P<0.01),the activity of CaN in myocardial tissue was increased(P<0.01),the p-NFAT3/NFAT3 radio was decreased(P<0.01),and the expression of GATA4 protein was increased(P<0.01).Compared with model group,the level of NT-pro BNP in serum was decreased in low dose group of ECYXT,medium dose group of ECYXT,high dose group of ECYXT and losartan potassium group(P<0.01),the LVEF was increased(P<0.01),the whole blood high shear viscosity,whole blood low shear viscosity,and plasma viscosity were decreased(P<0.01),the left ventricular mass index was decreased(P<0.01),the activity of CaN in myocardial tissue was decreased(P<0.01),the p-NFAT3/NFAT3 radio was increased(P<0.01),and the expression of GATA4 protein was decreased(P<0.01).Conclusion:ECYXT can inhibit the CaN-NFAT3-GATA4 signaling pathway in CHF rabbits with heart-qi deficiency complicated blood stasis and edema syndrome,improve the ventricular remodeling and cardiac function.