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目的研究川芎嗪(tetramethylpyrazine,TMP)对在体大鼠压力超负荷所致左心室肥厚的保护作用。方法采用腹主动脉缩窄法制备大鼠心肌肥厚模型。随机分为假手术组、模型组、TMP低、中、高3个剂量组(25,50,100 mg.kg-1)及左旋精氨酸组。术后给药3周,监测大鼠心功能,测量左室重量指数(左室重/体质量,LVHI=LVW/BW)和左室重/右室重(LVW/RVW)比率,测定左室心肌纤维直径(MD);通过实时荧光定量PCR检测心房利钠因子(ANF)和钙调神经磷酸酶(CaN)mRNA的表达。结果与模型组比较,TMP可显著降低左室舒张末压(LVEDP)而增加左心室最大收缩/舒张速率(±dp/dtmax),减小LVHI、LVW/RVW及MD,降低ANF和CaN mRNA的表达。结论川芎嗪对压力超负荷所致大鼠心肌肥厚具有保护作用,其机制可能与其抑制CaN信号通路有关。
Objective To study the protective effect of tetramethylpyrazine (TMP) on left ventricular hypertrophy induced by pressure overload in rats. Methods The rat model of cardiac hypertrophy was established by abdominal aorta constriction. Randomly divided into sham operation group, model group, TMP low, middle and high dose groups (25, 50, 100 mg.kg-1) and L-arginine group. The left ventricular mass index (left ventricular mass / body mass, LVHI = LVW / BW) and left ventricular mass / LVW / RVW ratio were measured after 3 weeks of administration. The diameter of myocardial fibers (MD) was measured. The expression of atrial natriuretic factor (ANF) and calcineurin (CaN) mRNA were detected by real-time fluorescence quantitative PCR. Results Compared with model group, TMP significantly decreased left ventricular end diastolic pressure (LVEDP) and increased left ventricular maximum systolic / diastolic velocity (± dp / dtmax), decreased LVHI, LVW / RVW and MD, decreased ANF and CaN mRNA expression. Conclusion Tetramethylpyrazine has a protective effect on myocardial hypertrophy induced by pressure overload in rats, which may be related to its inhibition of CaN signaling pathway.