基于NCX/SERCA2a平衡假说探讨燧心胶囊对心肌梗死后心衰大鼠的心肌保护作用

Study on the Myocardial Protective Effect of Suixin Capsule on Rats with Heart Failure after Myocardial Infarction Based on NCX/SERCA2a Equilibrium Hypothesis

目的观察燧心胶囊对心肌梗死后心衰(HF)大鼠的心肌保护作用,并初步探究作用机制。方法将大鼠分为假手术组、模型组及燧心胶囊低、中、高剂量组、阳性药物组(卡托普利),观察大鼠心肌组织形态学和心肌组织梗死体积变化;检测大鼠心室功能、血清中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)水平、心肌组织中钠钙交换蛋白(NCX)、肌浆网钙泵2a(SERCA2a)、Bcl-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)、Cleaved-Cas-pase-3蛋白表达。结果与假手术组比较,模型组左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、心肌梗死体积比例、左心室质量指数(LVMI)、心肌细胞凋亡率、AngⅡ、ALD及NCX、Bax、Cleaved-Caspase-3蛋白表达升高,左室收缩期后壁厚度(LVPWDs)、左心室射血分数(LVEF)、左室缩短分数(LVFS)及SERCA2a、Bcl-2蛋白表达降低(P <0.05)。与模型组比较,燧心胶囊各组与阳性药物组LVEDD、LVESD、心肌梗死体积比例、LVMI、心肌细胞凋亡率、AngⅡ、ALD及NCX、Bax、Cleaved-Caspase-3蛋白表达均显著降低,LVPWDs、LVEF、LVFS及SERCA2a、Bcl-2蛋白表达均显著升高(P <0.05)。与阳性药物组比较,燧心低剂量组LVEDD、AngⅡ、ALD及燧心低、中剂量组LVESD、心肌梗死体积比例、心肌细胞凋亡率、Bax、Cleaved-Caspase-3及燧心胶囊各剂量组NCX均显著升高,燧心胶囊各剂量组SERCA2a及燧心低、中剂量组LVEF、Bcl-2均显著降低(P <0.05)。燧心胶囊各剂量组LVEDD、LVESD、心肌梗死体积比例、心肌细胞凋亡率、AngⅡ及NCX、Bax、Cleaved-Caspase-3随剂量增加呈下降趋势,LVEF、SERCA2a、Bcl-2则呈上升趋势。结论燧心胶囊对心肌梗死后心衰大鼠的心肌具有保护作用,其作用可能通过恢复NCX/SERCA2a平衡,从而降低心肌梗死引起的组织损伤和细胞凋亡来实现的。

Objective:To explore the myocardial protective effect of Suixin Capsule on rats with heart failure(HF)after myocardial infarction,and to explore its mechanism. Methods:Rats were divided into sham operation group,the model group,low,medium,and high dose groups of Suixin Capsule and positive drug group(Captopril).The changes of myocardial morphology and infarct volume were observed,and the protein expression of ventricular function,AngⅡ,ALD,NCX,SERCA2a,Bax,Bcl-2 and Cledved-Caspase 3 were detected. Results:Compared with sham operation group,LVEDD,LVESD,volume ratio of myocardial infarction,LVMI,apoptotic rate of myocardial cells and the protein expressions of AngⅡ,ALD and NCX,Bax and Ccleaved-Caspase 3 in the model group increased,and LVPWDs,LVEF,LVFS and the protein expression of SERCA2a and Bcl-2 decreased(P < 0.05).Compared with the model group,LVEDD,LVESD,volume ratio of myocardial infarction,LVMI,apoptotic rate of myocardial cells,AngⅡ,ALD and the protein expression of NCX,Bax and Cleaved-Caspase 3 significantly decreased in Suixin Capsule group and the positive drug group,while LVPWDs,LVEF,LVFS and the protein expression of SERCA2a and Bcl-2 significantly increased(P < 0.05). Compared with the positive drug group,LVEDD,AngⅡ,ALD in low dose Suixin Capsule group,and LVESD,volume ratio of myocardial infarction,apoptotic rate of myocardial cells Bax,cleaved-caspase 3 and NCX in low and medium dose of Suixin Capsule groups and NCX in each dose group of Suixin Capsule increased significantly;SERCA2a in each dose group of Suixin Capsule and LVEF,Bcl-2 in low and medium dose of Suixin Capsule group significantly decreased(P < 0.05). LVEDD,LVESD,volume ratio of myocardial infarction,apoptotic rate of myocardial cells,AngII and NCX,Bax,cleaved-caspase 3 in each dose group of Suixin Capsule showed a downward trend with the increase of dose,while LVEF,SERCA2a and Bcl-2 showed an upward trend. Conclusion:Suixin Capsule has a protective effect on myocardium of rats with heart failure after myocardial infarction. Its effect may be achieved by restoring the balance of NCX/SERCA2a,thereby reducing tissue damage and cell apoptosis caused by myocardial infarction.