丹参酮对肥厚心肌L-型钙电流的影响

The Effect of Tanshinone on L-type Calcium Current in Hypertrophic Myocardium

目的心肌肥厚是导致心力衰竭、心律失常和猝死的高危因素。丹参酮已被证实能够有效地拮抗心肌肥厚的发生,但是对于其能否改变肥厚心肌上存在的电生理异常尚不清楚。方法本实验拟通过膜片钳和胞内钙测定技术,观察比较丹参酮和卡托普利对“一肾一夹”手术导致的肥厚心肌细胞膜上动作电位时间、L型钙通道电流和胞内钙离子浓度的影响,来阐明丹参酮预防心脏肥厚发生心律失常可能的电生理基础。结果丹参酮可以显著的缩短肥厚心肌细胞中存在的动作电位时间延长(P<0.001)、降低膜电容和ICa,L峰值幅度(P<0.001),但不影响ICa,L密度,并能够显著减少胞内钙离子浓度。结论丹参酮能够在抗心肌肥厚的同时通过减少钙内流、缩短动作电位时间,起到预防心律失常的作用。

Objective Myocardial hypertrophy is the high risk factor for heart failure, arrhythmia and sudden death. It has been demonstrated that Tanshinone could effectively inhibit the onset of myocardial hypertrophy, but the effect of Tanshinone on the electrophysiological abnormality in cellular membrane of hypertrophic myocardium is unknown. Methods The hypertrophic cardiomyocytes were isolated from hypertrophied left ventricles in 1K1C rats. Captopril（25 mg/kg by garage） and or Tanshinone（ 10 mg/kg IP） were administered for 8 weeks after the 1K1C model being established for 6 weeks. By using patch clamp and intra-cellular calcium survey technique, the effect of Tanshinone and captopril on the action po- tential duration, L-type calcium current （Ic,.u） and intra-cellular calcium ion concentration in cellular mem- brane was investigated. Results Tanshinone markedly shortens the prolongated action potential duration in hypertrophied myocytes （P〈0.001）, decreases membrane capacity and peak amplitude of ICa,L （P〈0.001）. Moreover, Tanshinone significantly reduces intra-cellular calcium ion concentration, with no effect on the density of ICa,L, Conclusion Tanshinone not only reverses the myocardial hypertrophy, but also reduces calcium influx and shorten action potential duration which are beneficial to prevent arrhythmia.