燧心胶囊对慢性心力衰竭大鼠保护作用及机制研究

Protective Effects and Mechanism of Suixin Capsule on Chronic Heart Failure Rats

目的:探究燧心胶囊对慢性心力衰竭(CHF)大鼠的保护作用及机制。方法:将50只雄性SD大鼠随机分为5组:假手术组(A组)、模型组(B组)、燧心胶囊高剂量(10.8 g/kg)组(C组)、燧心胶囊低剂量(2.7 g/kg)组(D组)、卡托普利(5.83 mg/kg)组(E组)。连续给药12周后,测定各组大鼠心输出量,血流动力学监测左室收缩压(LVESP)、左室舒张压(LVEDP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dtmax),心肌组织钠钙交换蛋白(NCX)及肌浆网钙泵2a(SERCA2a)蛋白行IHC染色,利用PCR及Western Blot(WB)实验检测心肌组织中NCX和SERCA2a mRNA及蛋白表达量。结果:①与A组比较,B组NCX蛋白表达量增多,SERCA2a蛋白表达量减少;心输出量降低(P<0.05);左心室收缩末期内径LVESP及左心室舒张末期内径LVEDP均显著升高(P<0.05),±dp/dtmax明显减慢(P<0.05);NCX mRNA及蛋白表达量增多(P<0.05),SERCA2a mRNA及蛋白表达量减少(P<0.05)。②与B组比较,C组、E组NCX蛋白表达量减少,SERCA2a蛋白表达量增多;心输出量增多(P<0.05),LVESP及LVEDP均显著降低(P<0.05),±dp/dtmax明显升高(P<0.05);NCX mRNA及蛋白表达量减少(P<0.05),SERCA2a mRNA及蛋白表达量增多(P<0.05)。③D组大鼠上述结果与B组大鼠比较,差异无统计学意义(P> 0.05)。结论:燧心胶囊对慢性心力衰竭大鼠心肌组织具有保护作用,可通过下调NCX的表达、上调SERCA2a的表达,调节CHF大鼠的心室舒缩功能。

Objective:To explore the protective effect and mechanism of Suixin capsule on chronic heart failure(CHF) rats. Methods :Fifty male SD rats were randomly divided into five groups:sham operation group(group A),model group(group B),Suixin capsule high dose group(10.8 g/kg)(group C) and Suixin capsule low dose group(2.7 g/kg)(group D),captopril group(5.83 mg/kg)(group E). After 12 weeks of continuous administration,cardiac output,left ventricular systolic pressure(LVESP),left ventricular diastolic pressure(LVEDP),maximum rate of rise of left ventricular pressure(+ dp/dtmax) and maximum rate of decrease of left ventricular pressure(-dp/dtmax)were measured and the pathological changes of myocardial tissue were observed after sodium-calcium exchanger(NCX) and SERCA2 a IHC staining. The expression of NCX and SERCA 2 a in myocardial tissue was detected by PCR and WB. Results :(1)Compared with group A,the level of NCX was increased in group B. Then,the level of SERCA2 a and cardiac output were decreased(P< 0.05),LVESP and LVEDP increased significantly(P< 0.05),±dp/dtmaxdecreased significantly(P< 0.05) in group B. Finally,the expression of NCX mRNA and protein was higher in group B than A(P< 0.05),and the expression of SERCA2 a mRNA and protein was lower in group B than A(P< 0.05).(2)Compared with group B,the level of NCX was decreased in group C and E. Then,the level of SERCA2 a and cardiac output were increased(P< 0.05),LVESP and LVEDP decreased significantly(P< 0.05),±dp/dtmaxincreased significantly(P< 0.05) in group B.Finally,the expression of NCX mRNA and protein was lower in group C and E than group A(P< 0.05),and the expression of SERCA2 a mRNA and protein was higher in group C and E than group A(P< 0.05).(3)The results of group B and group D showed no significant difference(P> 0.05). Conclusion:Suixin capsule has the protective effect on myocardial tissue in CHF rats,and it can regulate the ventricular function of in CHF rats by down-regulating the expression of NCX and up-regulating the expression of SERCA2 a.