川芎嗪对大鼠压力超负荷型心肌肥厚的保护作用

Protective Effects of Tetramethylpyrazine Against Myocardial Hypertrophy Induced by Pressure Overload in Rats

关键词:  川芎嗪  左心室肥厚  腹主动脉缩窄  钙调神经磷酸酶  大鼠

Key words:  tetramethylpyrazine  left ventricular hypertrophy  abdominal aorta coarctation  calcineurin  rat

摘要:

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。

Abstract:

OBJECTIVE To investigate the protective effects of tetramethylpyrazine(TMP) on myocardial hypertrophy induced by pressure overload in rats in vivo. METHODS Myocardial hypertrophy model of the rats induced by pressure overload was prepared by constricting abdominal aorta. The operated rats were randomly divided into abdominal aorta constricted model group, three dosage of TMP groups (25, 50, 100 mg·kg^-1) and L-arginine group. The abdominal aorta was not constricted in sham operated control group. The drugs were administered on the next day of operation, and continued for 3 weeks, the cardiac function was assessed. The ratios of left ventricular weight to body weight (LVHI=LVW/BW), left ventricular weight to right ventricular weight (LVW/RVW) and the cardio-myocyte diameters (MD) after dyeing by hematoxylin-eosin were measured. The expressions of aterial natriuretic peptide (ANF, a marker of myocardial hypertrophy) and calcineurin (CaN) mRNA was detected at the transcript levels by real time-PCR. RESULTS Compared with abdominal aorta constricted model group, TMP significantly reduced LVHI, LVW /RVW, MD and left ventricular end-diastolic pressure (LVEDP), but increased ±dp/dtmax, the expressions of ANF and CaN mRNA were significantly suppressed by TMP. CONCLUSION TMP has protective effects on the left ventricular hypertrophy induced by overload pressure in rats, which may be, in partly, mediated by its inhibitory effect on CaN signaling pathway.