健心颗粒对慢性心衰大鼠心功能的影响及其可能机制

Effects and possible mechanism of jianxin granules on cardiac function in rats with chronic congestive heart failure

目的:探讨健心颗粒对慢性心衰大鼠心功能的影响及可能机制。方法:32只大鼠随机分为假手术组、模型组、健心颗粒组和苯那普利组。采用缩窄腹主动脉法制备慢性心衰大鼠模型。造模后第13周开始灌胃给药,连续给药12周后,测定大鼠在体血流动力学指标:左室内压最大上升及下降速率(±dP/dt_(max))、左室舒张末期压(LVEDP),并计算左心室质量指数(LVMI)。采用RT-PCR、Western blot方法分别检测左室组织肌浆网Ca^(2+)-ATP酶(SERCA2a)mRNA及其蛋白质的表达。用饱和苦味酸天狼星红染色分析间质的胶原容积分数(CVF),并估计心肌纤维化程度。结果:模型组的LVMI、LVEDP均显著高于假手术组大鼠(均P<0.01);而模型组的±dP/dt_(max)比假手术组明显降低(P<0.01)。健心颗粒及苯那普利干预组均能降低慢性心衰大鼠的LVMI、LVEDP,增加±dP/dt_(max)(均P<0.01);与假手术组比较,模型组大鼠左心室SERCA2a基因表达下调,CVF明显增加(均P<0.05)。健心颗粒及苯那普利均能上调模型组大鼠SERCA2a表达,使左心室内膜及心肌小动脉周围的胶原生成减少(均P<0.05)。结论:健心颗粒能改善慢性心衰大鼠心功能,具有抗心室重构的作用,其机制可能与上调心肌SERCA2a表达、抑制心肌纤维化有关。

AIM： To investigate the effects of jianxin granules on cardiac performance in rats with chronic congestive heart failure and the possible mechanism. METHODS： Animal models of heart failure were induced by clipping the abdominal aorta. Thirty two rats were randomly divided into four groups： sham operated （sham） group, aortic stenosis （model） group, jianxin granules group, and benazepril group. Drugs were administered intragastrically from the 13th week after surgery and rats were examined after 12 weeks＇ treatment. Hemodynamic parameters （ including _＋ dP/dtmax and LVEDP） and the ratio of left ventricle （LV） to body weight（LVMI） were determined. SERCA2a mRNA and protein expression were assessed by RTPCR and Western blot techniques, respectively, and interstitial collagen volume fraction （CVF） was evaluated by picrosirus red staining. RESULTS： LVMI and LVEDP significantly increased and _＋ dP/dtmax decreased in model rats. Both jianxin granules and benazepril medication reversed these effects. SERCA2a expression was downregulated and CVF significantly increased in the model group com pared with those in sham control group. Jianxin granules and benazepril treatment upregulated SERCA2a expression and suppressed CVF compared with those in model rats. CONCLUSION： Jianxin granulesimprove myocardial function, which may result from its upregulation of SERCA2a expression and amelio ration of myocardial fibrosis in rats with chronic congestive heart failure.