薯蓣皂苷对大鼠心肌收缩力影响的研究  

Effects of dioscin on rat myocardial contractility

作　　者：韩钰[1] 杨帆[1] 丛恬駪[1] 孙凯[1] 李燕[1] 康毅[1] 尹永强[1] 娄建石[1] 

机构地区：[1]天津医科大学基础医学院药理学教研室,天津300070

出　　处：《中国药理学通报》2016年第2期258-262,共5页Chinese Pharmacological Bulletin

基　　金：天津应用基础及前沿技术研究计划青年项目(No14JCQNJC13700)

摘　　要：目的观察薯蓣皂苷(dioscin,Dio)对大鼠心肌收缩力的影响。方法采用Langendorff逆行主动脉灌流法对大鼠离体心脏进行灌流,利用压力感受器插管法测定左心室相关心功能参数,记录低、中和高3个浓度Dio对左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室内压最大上升/下降速率(±dp/dt_(max))的影响。利用激光共聚焦显微镜观察Dio对H9c2细胞内Ca^(2+)浓度的影响,并利用多功能酶标仪观察药物对细胞线粒体膜电位的影响。结果 0.1、1μmol·L^(-1)Dio可明显增加LVSP,由(11.55±0.52)、(10.53±0.28)kPa分别增加至(13.08±0.72)、(12.53±0.64)kPa(P<0.01);增加+dp/dt_(max)由(0.38±0.10)、(0.40±0.07)kPa·ms^(-1)分别增加至(0.42±0.11)、(0.43±0.02)kPa·ms^(-1)(P<0.05)。10μmol·L^(-1)Dio则使LVSP由(12.13±0.33)kPa减至(9.46±0.77)kPa(P<0.01),使+dp/dt_(max)由(0.42±0.04)kPa·ms^(-1)降为(0.24±0.04)kPa·ms^(-1)(P<0.01)。0.1、1、10μmol·L^(-1)的Dio可使H9c2细胞中Ca^(2+)相对荧光强度由(16.62±0.89)分别增加至(21.48±0.80)、(25.68±0.69)和(19.84±0.66)(P<0.01)。0.1、1μmol·L^(-1)Dio对H9c2细胞线粒体膜电位无明显影响,而10μmol·L^(-1)Dio会使JC-1单体与聚合物的比值由(1.14±0.03)增加为(1.35±0.06)(P<0.01),即引起线粒体膜电位下降。结论低、中浓度Dio可增加LVSP和+dp/dt_(max),表现正性肌力作用,机制为增加细胞内Ca^(2+)浓度。并且,其在增加细胞内Ca^(2+)浓度的同时并不会引起钙超载,仅高浓度出现。Aim To investigate the effects of dioscin(Dio) on rat myocardial contractility.Methods Left ventricular contractile function was measured using the Langendorff non-recirculating mode of isolated rat heart perfusion.Effects of low,middle and high concentration of Dio were investigated by measuring left ventricular systolic pressure(LVSP) and left ventricular end diastolic pressure(LVEDP).Also,peak rates of rise /fall of left ventricular pressure(±dp/dt_(max)) of isolated rat heart were calculated.Effects of Dio on intracellular free calcium concentration in rat H9c2 cells were measured by using the confocal microscopy.Mitochondrial membrane potential was detected with multifunctional microplate reader.Results With 0.1,1 μmol·L^(-1) Dio,LVSP were significantly enhanced from(11.55±0.52),(10.53±0.28) kPa to(13.08±0.72),(12.53±0.64) kPa(P<0.01);±dp/dt_(max)were dramatically increased from(0.38±0.10),(0.40±0.07) kPa · ms^(-1) to(0.42±0.11),(0.43± 0.02) kPa · ms^(-1)) P <0.05).With the 10 μmol ·L^(-1) Dio,LVSP and +dp/dt_(max) were both decreased from(12.13±0.33) kPa and(0.42±0.04) kPa ·ms^(-1) to(9.46±0.77) kPa and(0.24±0.04) kPa· ms^(-1)(P < 0.01).With 0.1,1,10 μmol · L^(-1)Dio,the relative fluorescence intensity of intracellular free calcium concentrations was increased significantly from(16.62±0.89) to(21.48 ±0.80),(25.68±0.69) and(19.84±0.66)(P < 0.01) respectively.0.1,1 μmol·L^(-1) Dio showed no significant effects on the mitochondrial membrane potential of rat H9c2 cells,while with effects of 10 μmol · L^(-1) Dio,the ratio of JC-1 monomer and J-aggregates was changed from(1.14±0.03) to(1.35±0.06)(P<0.01),indicating a decrease in the mitochondrial membrane potential.Conclusion Low and middle concentrations of Dio show a positive inotropic effect on isolated rat heart,as the LVSP and +dp/dt_(max) are enhanced,which may concern with the increase of the intracellular concentration of Ca^(2+).It will not cause the calcium overload while the intracellular concentration of Ca^(2+)is inc

关 键 词：薯蓣皂苷 CA^2+浓度 正性肌力作用 离子通道 钠钙交换体 左心室收缩压 

分 类 号：R-332[医药卫生] R284.1