心复康丸对压力超负荷大鼠心肌组织microRNA-1影响的实验研究

Experimental study of Xinfukang pills on microRNA-1 in cardiac tissue of pressure overloaded rats

关键词:  心复康丸  microRNA-1  压力超负荷  心肌肥厚

Key words:  Xinfukang pill  microRNA-1  pressure overload  myocardial hypertrophy

摘要:

[目的]观察心复康丸对压力超负荷大鼠所致的心肌肥厚和心室重塑的干预作用，并研究其作用机制是否与影响心肌组织microRNA-1（miR-1）的表达有关。[方法]Wistar雄性大鼠采用腹主动脉缩窄的方法复制心肌肥厚和心室重塑的模型。术后4周，将模型动物随机分为模型组（M组）、依那普利组（E组）、心复康丸低剂量组（L组）、心复康丸高剂量组（H组）。假手术组（S组）不结扎腹主动脉，其他处理相同。分别于术后8、12周，Masson染色观察心肌组织的胶原容积分数。免疫组织化学法检测心肌组织中钙离子ATP酶（SERCA2）、Fibullin-2蛋白表达的变化。实时聚合酶链反应（PCR）法检测心肌组织miR-1表达的改变。[结果]术后8、12周各时间点，与M组比较，E组和H组大鼠心肌纤维化面积显著减少（P<0.01）。术后8、12周各时间点，与M组比较，H组心肌组织Fibullin-2显著降低（P<0.01），SERCA2显著升高（P<0.01），miR-1表达显著升高（P<0.01），L组仅在8周时心肌组织Fibullin-2的表达有明显改变（P<0.05）。[结论]心复康丸可能通过促进miR-1表达，调控其靶因子Fibullin-2蛋白，抑制心肌纤维化，进而在抑制心肌肥厚和心室重构的过程中发挥作用。

Abstract:

[Objective] To explore improving effect of Xinfukang pills on pressure overload-induced myocardial hypertrophy and ventricular remodeling in rats, the relationship between its pharmacology effect and the express of miR-1 and in cardiac tissue was evaluated.[Methods] The experiment adopted the method of narrowing and contraction the aorta in adult and healthy male Wistar rats to establish the model of animals with myocardial hypertrophy and ventricular remodeling. Four weeks after coarctation of abdominal aorta, the Wistar rats were randomly divided into model group (M group), Enalapril group(E group), Xinfukang pills low dose group(L group) and Xinfukang pills high dose group (H group). Sham surgery group did not ligate the abdominal aorta, other treatments were same as others. 8 and 12 weeks after surgery, myocardial tissue collagen volume fraction was evaluated by Masson dyeing. The express of SERCA2 and Fibullin-2 in cardiac tissue were detected by immunohistochemistry. The express of miR-1 was also detected by Real time PCR. [Results] The 8 and 12 weeks after surgery, compared with group M, the myocardial fibrosis area of group E and H were reduced significantly (P<0.01), and the express of Fibullin-2 in the cardiac tissue of group H was decreased significantly (P<0.01). The express of SERCA2 in the cardiac tissue of group H was increased significantly (P<0.01). The express of miR-1 in the cardiac tissue of group H increased significantly (P<0.01). After 8 weeks, the express of Fibullin-2 in the cardiac tissue of group L was different with group M (P<0.05).[Conclusion] Xinfukang pills can increase the express of miR-1 and regulating the target protein Fibullin-2, therefore it may inhibit apoptosis of myocardial fibrosis, and plays an important role in repressing cardiac hypertrophy and ventricular remodeling process.