芪丹利心丸对心肌梗死后慢性心力衰竭大鼠心肌纤维化的影响

Effect of Qidan Lixin Pill on myocardial fibrosis in rats with chronic heart failure after myocardial infarction

关键词:  转化生长因子-β1/Smads信号通路  益气活血利水  芪丹利心丸  心肌梗死  慢性心力衰竭  心肌纤维化

Key words:  TGF-β1/Smads signaling pathway  Yiqi Huoxue Lishui  Qidan Lixin Pill  myocardial infarction  chronic heart failure  myocardial fibrosis

摘要:

[目的] 观察芪丹利心丸对心肌梗死后慢性心力衰竭大鼠心肌纤维化的影响。[方法] 通过结扎大鼠左冠状动脉（冠脉）前降支的方法诱导形成慢性心力衰竭模型，经过芪丹利心丸药物[1.1、2.2、4.4 g/（kg·d）]4周干预后，利用超声心动仪和左心室压力-容积环检测评价心功能。采用Masson染色观察各组心脏病理学变化，采用反转录-聚合酶链反应（RT-PCR）测定各组胶原蛋白（Collagen I和Ⅲ）的mRNA水平，采用蛋白质免疫印迹实验（Western Blot）检测各组转化生长因子-β1（TGF-β1）、Smad3、Smad7的蛋白表达水平。[结果] 模型组心功能显著下降[左室射血分数（LVEF）、左室短轴缩短率（LVFS）、左室内压上升或下降最大速率（±dp/dt max），P<0.05]，心室重构明显[室间隔厚度（IVST）、左室收缩末期内径（LVESD），P<0.05]；与模型组比较，芪丹利心丸能够明显改善慢性心力衰竭大鼠心功能，延缓心室重构进程，其中芪丹利心丸中剂量组和芪丹利心丸高剂量组效果较为明显（P<0.05），并且抑制胶原蛋白CollagenI和Ⅲ的mRNA表达（P<0.05），减少心肌纤维细胞形成，下调心肌纤维化相关蛋白TGF-β1、Smad3蛋白表达（P<0.05），提高抗纤维化蛋白Smad7水平（P<0.05）。[结论] 益气活血利水方芪丹利心丸能改善心肌梗死后慢性心力衰竭大鼠心功能，延缓心室重构和心肌纤维化水平，其机制可能与调控TGF-β1/Smads的信号通路有关。

Abstract:

[Objective] To study the effect of Qidan Lixin Pills (QD) on myocardial fibrosis in rats with chronic heart failure (CHF) after myocardial infarction (MI).[Methods] CHF was induced by the left anterior descending artery ligation (LAD) in adult male Sprague-Dawley rats. After 4 weeks of intervention with QD (1.1,2.2,4.4 g/kg·d),cardiac function indexes were measured by echocardiography and pressure volume system. The masson staining was used to compare the changes of pathological fibrosis in each group. The mRNA levels of collagen I and collagen III in each group were measured by RT-PCR. Western blot was used to detect the expression of TGF-β1,Smad3 and Smad7 proteins.[Results] At the end of the experiment,the indexes of cardiac function (LVEF,LVFS,+dp/dt max,-dp/dt max) were significantly reduced in model group (P<0.05). The ventricular remodeling was obviously changed. The QD can improve the cardiac function and delay the process of ventricular remodeling of chronic heart failure rats. Among them,the improvement of cardiac function was more obvious in the middle-dose group and high-dose group,and ventricular remodeling was relieved (P<0.05). QD also inhibited the expression of Collagen I and III (P<0.05),reduced the formation of myocardial fibroblasts,down-regulated the expression of myocardial fibrosis related proteins TGF-β1 and Smad3 (P<0.05),and increased the level of anti-fibrosis protein Smad7 (P<0.05).[Conclusion] Yiqi Huoxue Lishui Prescription (Qidan Lixin Pills) can improve cardiac function in chronic heart failure rats after myocardial infarction,delay ventricular remodeling and myocardial fibrosis. Its mechanism may be related to regulating TGF-β1/Smads signaling pathway.