益心泰有效组分对慢性心力衰竭兔左室肥厚和心肌细胞凋亡的干预作用及机制研究

Effect of Effective Components of Yixintai(益心泰)on Left ventricular Hypertrophy and Cardiomyocyte Apoptosis in Rabbits with Chronic Heart Failure and Its Mechanism

目的:研究益心泰有效组分对慢性心力衰竭兔左室肥厚和心肌细胞凋亡的干预作用及其机制。方法:120只新西兰兔随机抽取20只作为假手术对照组,剩余100只采用腹主动脉缩窄法+丙基硫氧嘧啶灌胃建立兔慢性心衰模型。将造模成功的兔随机分为模型对照组、益心泰有效组分2.1、4.2、8.4 g/kg组、氯沙坦钾2.75 mg/kg组,模型对照组和假手术对照组给予等体积的蒸馏水灌胃,1次/d,共干预4 w。比较干预后各组兔心肌组织形态学,血清氨基末端B型利钠肽(NT-pro BNP)含量,心脏超声指标,血流动力学指标,左心室质量指数,心肌细胞凋亡情况,心肌组织c-Jun氨基端激酶(Cjun)、血清应答元件(Cfos)mRNA及蛋白表达。结果:与假手术对照组比较,模型对照组血清NT-pro BNP含量显著升高(P<0.01),左心室射血分数(LVEF)及左心室收缩压(LVSP)显著下降,左心室后壁厚度(LVPWT)及左心室舒张末期压(LVEDP)显著升高,左心室质量指数及心肌细胞凋亡指数显著升高(P<0.01),心肌组织Cjun、Cfos mRNA及蛋白表达显著上调(P<0.01);与模型对照组比较,各给药组血清NT-pro BNP含量显著降低(P<0.01),LVEF、LVSP显著升高,LVPWT、LVEDP均显著降低,心肌细胞凋亡指数显著下降(P<0.01),心肌组织Cjun、Cfos mRNA及蛋白表达明显下调(P<0.05或P<0.01);益心泰有效组分4.2、8.4 g/kg组和氯沙坦钾2.75 mg/kg组左心室质量指数显著降低(P<0.01)。结论:益心泰有效组分可抑制慢性心衰兔心肌组织Cjun、Cfos mRNA及蛋白表达,减轻左室肥厚及心肌细胞凋亡,改善心衰。

Objective:To study the effect of effective components of Yixintai(益心泰)on left ventricular hypertrophy and cardiomyocyte apoptosis in rabbits with chronic heart failure(CHF)and its mechanism.Methods:Twenty New Zealand rabbits were randomLy selected from 120 rabbits as the sham operation group,and the remaining 100 rabbits were used to establish the rabbit model of CHF by coarctation of the abdominal aorta and intragastric administration of propylthiouracil.The rabbits successfμLly modeled were randomLy divided into a model control group,2.1 g/kg,4.2 g/kg,and 8.4 g/kg of Yixintai effective components groups,and a 2.75 mg/kg losartan potassium group.An equal volume of distilled water was orally administrated to rabbits in the model control group and sham operation control group,once per day,for 4 weeks.After treatment,the myocardial pathological structure,the level of N-terminal B-type natriuretic peptide(NT-pro BNP)in the serum,cardiacμLtrasound parameters,hemodynamic parameters,left ventricular mass index,cardiomyocyte apoptosis,and the protein and mRNA expression levels of c-Jun N-terminal kinase(Cjun),serum response element(Cfos)in myocardial tissues were observed.Results:As compared with the sham operation group,the serum level of NT-pro BNP in the model control group was significantly increased(P<0.01),the left ventricular ejection fraction(LVEF)and the left ventricular systolic pressure(LVSP)were decreased(P<0.01),the left ventricular posterior wall thickness(LVPWT)and the left ventricular end-diastolic pressure(LVEDP)were increased(P<0.01),the left ventricular mass index and the cardiomyocyte apoptosis were increased(P<0.01),and the protein and mRNA expression of Cjun and Cfos in myocardial tissues were up-regulated(P<0.01).As compared with the model control group,the serum level of NT-pro BNP in each treatment group was significantly decreased(P<0.01),the LVEF and the LVSP were increased(P<0.01),the LVPWT and the LVEDP were decreased(P<0.01),the cardiomyocyte apoptosis were decreased(P<0.01),and the protein and mRNA expression of Cjun and Cfos in myocardial tissues were down-regulated(P<0.05,P<0.01).The left ventricular mass index in the 2.75 mg/kg losartan potassium group and 4.2 g/kg and 8.4 g/kg of Yixintai effective components groups were significantly decreased(P<0.01).Conclusion:The effective components of Yixintai can inhibit the protein and mRNA expressions of Cjun and Cfos in myocardial tissues of rabbits with CHF,reduce left ventricular hypertrophy and cardiomyocyte apoptosis,and improve heart failure.