川芎嗪对DHF大鼠心肌损伤的保护作用及其机制研究

Studies on protection and mechanism of tetramethylpyrazine on myocardial injury of rats with DHF

目的:观察川芎嗪(TMP)对舒张性心力衰竭(DHF)大鼠心肌损伤及心肌细胞内钙超载的影响。方法:腹主动脉缩窄法建立DHF模型,术后4周随机分为模型组、TMP高、中、低剂量组(40,20,10 mg.kg-1.d-1)4组(n=10),另有假手术组10只。连续给药4周后应用十六导生理记录仪测定血流动力学指标;采用透射电镜观察大鼠心肌病理改变及细胞超微结构。应用激光共聚焦扫描显微镜(LSCM)技术检测心肌细胞内[Ca2+]i变化;采用比色法测定心肌线粒体ATP酶活性。结果:与假手术组相比,模型组大鼠左心室收缩压(LVSP)、左室内压最大上升速率(+dp/dtm ax)无显著变化,左心室舒张末期内压(LVEDP)显著升高,左室内压最大下降速率(-dp/dtm ax)显著降低,左室松弛时间常数(T)数值显著延长;心肌损伤明显,肌细胞内Ca2+浓度明显上升,线粒体钙ATP酶活性明显下降。给药4周后,与模型组比较,TMP中、低剂量组显著降低LVEDP,显著升高-dp/dtm ax,显著缩短T;明显减轻心肌超微结构的损害;显著降低心肌细胞内荧光值;心肌细胞线粒体中Ca2+-ATPase活力明显增加。结论:中、低剂量的TMP可以明显减轻DHF所致的心肌损伤,改善DHF大鼠心功能及心肌细胞内[Ca2+]i,提高心肌线粒体ATP酶活性,拮抗钙超载。

Objective： To study the effects of different doses of tetramethylpyrazine on injury and calcium overload in myocardial cells of diastole heart failure rat model. Method： Diastole heart failure model was established by the coarctation of abdominal aorta. 4 weeks after operation, forty rats with DHF were divided into four groups randomly as follows, model （ physiological saline 2 mL）, tetramethylpyrazine （40 mg·kg^-1·d^-1）, tetramethylpyrazine （20 mg·kg^-1·d^-1）, tetramethylpyrazine （ 10 mg·kg^-1·d^-1）, with 10 rats for each group （n = 10）, and 10 sham operation rats was taken as control（ physiological saline, 2 mL）. After 4 weeks administration, cardiac function was determined by catheter. The changes of myocardial uhrastructure were investigated by means of transmission electron microscope. [ Ca^2＋ ]i was measured by laser scanning confocal microscope [ LSCM ]. Ca^2＋ -ATPase activity of mitochondrion was measured by the method of enzymatic reaction chromatometry. Result： Compared with the control group, the rats of operation group have no significant changes on left ventricular systolic pressure （LVSP） and maximal rising rate of ventricular pressure （ ＋ dp/dtmax ） , but left ventricular end diastolic pressure （LVEDP） increased markedly, maximal delining rate of ventricular pressure （ - dp/dtmax） decreased significantly, left ventricular relax time constant quantity （T） markedly extended, myocardial pathology injured markedly, [ Ca^2＋ ] i in cardiocyte increased markedly and the Ca^2＋ -ATPase activity of myocardial mitochondria decreased significantly in the model group. After 4 weeks administration, compared with the model group, LVEDP decreased significantly, - dp/dt increased markedly, T markedly shortened, myocardial uhrastructure damage were significantly reduced, fluorescent value decreased and Ca^2 ＋ -ATPase activity of mitochondrion increased significantly in TMP low-dose group and mid-dose group. Conclusion ： Low dosage of TMP can reduced myocardial pathology injury, increased Ca^2＋ -ATPase activity of myocardial mitochondria, improve cardiac function and [ Ca^2 ＋ ] i in cardiocyte and antagonise calcium overload of rats with DHF.