黄芩甙对大鼠心室肌细胞触发性心律失常的影响及其机制

Effects of baicalin on L-type calcium current and trigged arrhythmia in rat ventricular cardiomyocytes

目的研究黄芩甙对触发性心律失常的影响,探讨黄芩甙抗心律失常的机制。方法酶解法分离大鼠心室肌细胞,全细胞膜片钳技术记录黄芩甙作用前后的L型钙电流(ICa-L)的变化,外科手术得到心室乳头肌,标准玻璃微电极技术记录黄芩甙作用前后跨膜动作电位(TAP)的变化以及哇巴因诱发的延迟后除极(DAD)和触发活动(TA)的影响。结果①在电压钳制下,黄芩甙对ICa-L均有明显抑制作用,随浓度的增加,对ICa-L的抑制作用逐渐增强。10,20和40μmol/L的黄芩甙对ICa-L的最大电流密度抑制作用分别由15.8±1.2pA/pF减小到11.3±0.9,8.2±0.8,4.9±0.6pA/pF(P均<0.05)。黄芩甙对ICa-L的抑制作用具有非常好的量效性,半效抑制浓度为27.7±1.9μmol/L。显著上抬I-V曲线。②20μmol/L黄芩甙明显缩短动作电位时程,抑制哇巴因诱导的DAD和TA。结论黄芩甙能抑制触发性心律失常,这可能与黄芩甙抑制心肌细胞ICa-L内流,减少细胞内Ca2+超载有一定关系。

Objective To investigate the effects of baicalin on triggered activity（TA） arrhythmia Methods L-type calcium current（ICa-L） was recorded before and after baicalin via using whole-cell patch-clamp technique in enzymatically dissociated single rat ventricular myocytes. The transmembrane action potential（TAP） was performed before and after baicalin on rat papillary muscles by conventional glass microelectrode technique. Results （1）With voltage clamp way, baicalin significantly inhibited ICa-L. The biggest current density of ICa-L was decreased from 15.8 ±1.2 pA/pF to 1 1.3 ±0.9, 8.2 ±0.8 and 4.9 ±0.6 pA/pF respectively（ all P 〈0.01 ） by administration of baicalin （ 10, 20 and 40μmol/L）. Baicalin markedly blocked ICa-L with concentration-dependent relation with an IC50 value of 27.7 ±1.9 μmol/L. Moreover, baicalin shifted the I-V curve of ICa-L upwards with voltage-dependent, but didn＇ t change markedly the shape of I-V curve. （2）Baicalin （20μmol/L） significantly shortened ADP20, ADPs0and APDg0,but didn＇t apparently change other electrophysiological parameters of TAP in rat papillary muscles. Ouabain could apparently induced the delayed afterdepolarization （DAD） and TA under basic cycle length of 500 ms in rat papillary muscles. With addition of baicalin（20μmol/L）, DAD and TA were markedly inclined, which was difficult to be revoked by ouabain （ compared with ouabain group, P 〈 0.01 ）. Conclusion Baicalin significantly inhibits ICa-L and ouabain-induced DAD and TA in rat hearts. It might be concerned about that baicalin blocked influx of ICa-L, and decreased Ca^2＋ overload in cardiomyocytes.