小檗碱对DHF大鼠血流动力学和心肌细胞内钙离子浓度的影响

目的:观察小檗碱(Ber)对舒张性心力衰竭(diastole heart failure,DHF)大鼠血流动力学和心肌细胞内钙离子浓度[Ca²⁺]_i的影响。方法:Wistar大鼠腹主动脉缩窄法建立DHF模型;术后4周,模型大鼠随机分为DHF模型组,Ber高、中、低剂量组(63,42,21mg·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;用激光扫描共聚焦显微镜(LSCM)扫描用Fluo-3AM负载好的心肌细胞内的荧光强度(FI)来表示[Ca²⁺]_i。结果:模型组与假手术组比,左心室收缩压(LVSP)、左室内压最大上升速率(+dp/dt_max)无显著变化,左心室舒张末期内压(LVEDP)显著升高(P<0.01),左室内压最大下降速率(-dp/dt_max)显著降低(P<0.01),左室松弛时间常数(T)数值显著延长(P<0.01);心肌细胞内[Ca²⁺]_i明显增高(P<0.05)。与模型组比较,Ber高剂量组比中剂量组低剂量组更显著降低LVEDP,显著升高-dp/dt_max(P<0.01),显著缩短T(P<0.01),显著降低心肌细胞内[Ca²⁺]_i(P<0.01)。结论:Ber高剂量组可以明显改善DHF大鼠血流动力学和降低心肌细胞内[Ca²⁺]_i。

Effects of different dose berberine on hemodynamic parameters and [Ca2+]i of cardiac myocytes of diastole heart failure rat model

Objective:To study the effects of different doses of berberine on hemodynamic parameters and calcium ion concentration([Ca²⁺]_i)of diastole heart failure rat models.Method:The mouse models of diastole heart failure were made by the imcomplete ligation of abdominal aorta.Forty Wistar heart failure rats were divided randomly into four groups,with 10 for each group(n=10).Heart failure rats were treated according to different doses drugs as follows:Model(natrii chloride 2 mL),berberine(63 mg·kg^-1·d^-1),berberine(42 mg·kg^-1·d^-1),berberine(21 mg·kg^-1·d^-1)ig,for each of the four groups respectively,4 weeks after coarctation of ascending aorta operation;and 10 age matched sham operation group was taken as control(natrii chloridi,2 mL).After administration four weeks,cardiac function was determined by catheter.Isolate single cardiomyocytes of rat which were loaded with Ca²⁺-sensitive fluorescent indicator Fluo-3/AM.[Ca²⁺]_i represented by fluorescent intensity[FI] was measured by laser scanning cofocal microscope[LSCM].Result:The rats of operation group have no significant changes with those of the control on left ventricular systolic pressure(LVSP)and maximal rising rate of ventricular pressure(+dp/dt_max),left ventricular end diastolic pressure(LVEDP)was much higher in operation group(P<0.01),but maximal falling rate of ventricular pressure(-dp/dt_max)was depressed(P<0.01),left ventricular relax time constant quantity(T)was markedly extended(P<0.01).[Ca²⁺]_i level in carkiac muscle cell was elevated markedly(P<0.05).Compared with operation group,high dose of Ber can decrease LEVDP,improve(-dp/dt_max)(P<0.01),decurtate left ventricular relax time constant quantity(P<0.01)and decrease [Ca²⁺]_i level better than those of middle and low dose group(P<0.01).Conclusion:Berberine is an effective new potent drug for conspicuous symptom relief of heart failure with positive dose dependency and step down [Ca²⁺]_i of myocardial cell.