当归提取物对大鼠左心室肥厚的保护作用

Protection of Angelica sinensis extract against left ventricular hypertrophy of rats

目的观察当归提取物对腹主动脉缩窄所致大鼠左心室肥厚的保护作用,并探讨其可能的作用机制。方法将雄性SD大鼠随机分为假手术组,模型组,当归提取物低、中、高剂量(25、50、100 mg/kg)组及L-精氨酸(200 mg/kg)阳性对照组。除假手术组外,其他组大鼠采用腹主动脉缩窄法制备大鼠左心室肥厚模型,术后次日给药,每天给药1次,连续给药21 d。观察各组大鼠心肌肥厚参数及血流动力学指标改变;测定左心室心肌纤维直径(MD);电镜观察心肌组织超微结构改变;实时荧光定量PCR法检测心房利钠因子(ANF)及钙调神经磷酸酶(CaN)mRNA的表达;Western blotting检测左心室心肌钙调神经磷酸酶α-亚基(CnA)蛋白的表达。结果与假手术组比较,模型组大鼠左心室肥厚指数(LVHI)、左心室质量/右心室质量(LVW/RVW)及MD均显著提高,ANF、CaN mRNA及CnA蛋白表达明显上调;当归提取物可使LVHI显著降低,LVW/RVW趋于降低或明显降低,舒缩功能指标改善,并使ANF、CaN mRNA及CnA蛋白表达下调。结论当归提取物对腹主动脉缩窄所致大鼠左心室肥厚具有保护作用,其机制可能与抑制CaN信号转导通路有关。

Objective To investigate the protection of Angelica sinensis extract on the left ventricular hypertrophy （LVH） of rats and explore the possible mechanisms. Methods Male SD rats were randomly divided into Sham, model, and low-, mid-, and high-dose A. sinensis extract （25, 50, and 100 mg/kg）, and L-arginine （200 mg/kg） positive control groups. Except for Sham group, the rats with LVH were induced by abdominal aorta coarctation and were administered from the next day after surgery once daily for consecutive 21 d. Changes of cardiac hypertrophy parameters and hemodynamic indexes of rats were observed. Left ventricular myocardial fiber diameter （MD） was determined. Electron microscopy was used to observe the ultrastructure of myocardial tissue. RT-PCR was used to determine the mRNA expression of atrial natriuretic factor （ANF） and calcineurin phosphatase （CAN）. Western blotting was used to determine the expression of ct-subunit of calcineurin phosphatase （CnA）. Results Compared with Sham group, the left ventricular hypertrophy index （LVHI）, the left ventricular weight/right ventricular weight （LVW/RVW）, and MD were remarkably increased, the expression of ANF, CaN mRNA, and CnA protein was obviously elevated. A. sinensis extract could remarkably decrease LVHI, tend to or significantly decrease LVW/RVW, improve the indicators of systolic and diastolic function, and down-regulate the expression of ANF, CaN mRNA and CnA protein. Conclusion A. sinensis extract has the protection against LVH induced by abdominal aorta coarctation in rats, and the mechanism may be related to its inhibitory effects on CaN signaling pathway.