七叶皂苷钠对离体蛙心心脏功能的影响及其机制初探

Preliminary discussion on the effect of sodium aescinate on cardiac function of isolated frog heart and its mechanism

目的观察七叶皂苷钠对离体蛙心心肌收缩力和心率的影响,并初步探究其机制,为七叶皂苷钠新的用途和深入临床实践提供理论支持。方法根据斯氏蛙心插管方法,分别用10.84μmol/L、21.68μmol/L、43.37μmol/L、86.73μmol/L、173.46μmol/L的七叶皂苷钠对离体蟾蜍心脏灌流,采用BL-420生物机能实验系统记录心率和心肌收缩力;加入低钙、正常钙、高钙任氏液和1.10μmol/L维拉帕米、40.60μmol/L的艾司洛尔、 0.39μmol/L的肾上腺素,记录5 min后充分灌洗,然后分别加入低钙、正常钙、高钙任氏液以及1.10μmol/L维拉帕米、40.60μmol/L的艾司洛尔、0.39μmol/L的肾上腺素配制的43.37μmol/L的七叶皂苷钠,记录5 min心率和心肌收缩力的变化。结果 10.84μmol/L、21.68μmol/L、43.37μmol/L、86.73μmol/L的七叶皂苷钠对离体蛙心心率无明显影响(P均>0.05);10.84μmol/L、21.68μmol/L、43.37μmol/L、86.73μmol/L的七叶皂苷钠可使离体蛙心心肌收缩力逐渐升高,约1 min时达高峰,5 min时虽然收缩力有所降低但仍高于加药前(P<0.05);173.46μmol/L的七叶皂苷钠使离体蛙心心肌收缩力迅速降低,基线上移,对心脏呈现明显的抑制作用,最后蛙心停止跳动;低钙任氏液、1.10μmol/L的维拉帕米、40.60μmol/L的艾司洛尔对蛙心具有负性肌力作用,七叶皂苷钠能够拮抗其对心肌的抑制作用;高钙任氏液、0.39μmol/L的肾上腺素对离体蛙心具有正性肌力作用,七叶皂苷钠能够增强其对心脏的正性肌力作用。结论 10.84μmol/L、21.68μmol/L、43.37μmol/L、86.73μmol/L的七叶皂苷钠对离体蛙心心肌收缩力有促进作用,此兴奋作用具有药物浓度依赖性,且其兴奋心肌的作用机制可能与激活心肌细胞L-型钙通道和兴奋心肌β_1受体有关;173.46μmol/L的七叶皂苷钠能够明显抑制蛙心心肌收缩力;七叶皂苷钠对离体蛙心心率影响不大。

Objective It is to observe the effect of sodium aescinate on myocardial contractility and heart rate of isolated frog heart, and to explore its mechanism, thus to provide theoretical support for the new use and deep clinical practice of sodium aescinate. Methods According to the frog heart intubation method, the isolated frog hearts were perfused with 10.84 μmol/L, 21.68 μmol/L, 43.37 μmol/L, 86.73 μmol/L, and 173.46 μmol/L sodium aglycone. BL-420 biofunctional system was used to record heart rate and myocardial contractility;after addition of low calcium, normal calcium, high calcium Ren’s solution and 1.10 μmol/L verapamil, 40.60 μmol/L esmolol, 0.39 μmol/L adrenaline, they were recorded for 5 minutes and then were fully irrigated, then low calcium, normal calcium, high calcium Ren’s solution and 1.10 μmol/L verapamil, 40.60 μmol/L esmolol, 0.39 μmol/L adrenal gland 43.37 μmol/L sodium aescinate was prepared and the changes in heart rate and myocardial contractility were recorded for 5 min. Results 10.84 μmol/L, 21.68 μmol/L, 43.37 μmol/L and 86.73 μmol/L sodium aescinate had no significant effect on heart rate of isolated frogs ( P >0.05);10.84 μmol/L, 21.68 μmol/L 43.37 μmol/L, 86.73 μmol/L sodium aescinate could gradually increase the contractility of isolated frog heart muscle, reaching a peak at about 1min. Although the contractility was lower at 5min, it was still higher than that before dosing ( P <0.05);173.46 μmol/L sodium aescinate rapidly decreased the contractile force of isolated frog heart muscle, and the baseline was up-shifted, which showed obvious inhibition to the heart. Finally, the frog heart stopped beating;low calcium Ren’s solution, 1.10 mmol/L verapamil, 40.60 μmol/L esmolol had negative inotropic effect on frog heart, and sodium aescinate could antagonize its inhibition on myocardium;high calcium solution, 0.39 μmol/L adrenaline had a positive inotropic effect on the isolated frog heart, and sodium aescinate could enhance its positive inotropic effect on the heart. Conclusion 10.84 μmol/L, 21.68 μmol/L, 43.37 μmol/L and 86.73 μmol/L sodium aescinate can promote the contractility of isolated frog heart muscle. This excitatory effect is drug-dependent and the mechanism of excitatory myocardial action may be related to the activation of myocardial L-type calcium channel and excitatory myocardial β1 receptor;173.46μmol/L sodium aescinate can significantly inhibit the contractile force of frog heart;sodium aescinate has no obvious effect on heart rate of isolated frog.