摘要
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.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2009年第21期2808-2812,共5页
China Journal of Chinese Materia Medica