卡维地洛抑制大鼠起搏心肌细胞钙库超载诱导的钙释放  

Effect of carvedilol on store overload-induced Ca^(2+) release in rat pacing cardiomyocytes

作　　者：赵瑞富[1] 李成鹏[1] 娄蓉蓉[1] 张存泰[2] 解翠红[3] 王琳[1] 马业新[1] 周强[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院综合科,湖北武汉430030 [3]华中科技大学同济医学院附属同济医院急诊内科,湖北武汉430030

出　　处：《中国病理生理杂志》2014年第5期779-784,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81270240;No.81202531)

摘　　要：目的:探讨非选择性β受体阻滞剂卡维地洛对起搏心肌细胞钙库超载诱导钙释放(SOICR)的作用及其机制。方法:电刺激起搏大鼠单个心肌细胞并灌注异丙肾上腺素及咖啡因诱导钙库钙超载,从而触发肌浆网钙释放通道(兰尼碱受体2,RyR2)舒张期开放引起SOICR。应用钙离子荧光成像技术记录胞内钙浓度的实时变化。实验分为对照组、卡维地洛组、美托洛尔组、酚妥拉明组和硝苯地平组。结果:(1)与基线刺激时比较,对照组细胞灌注异丙肾上腺素和咖啡因后,起搏细胞钙瞬变振幅显著增高(P<0.01),SOICR的发生率显著增加(P<0.01)。(2)在1~4 Hz起搏频率下卡维地洛组细胞SOICR发生率分别为2.00%、6.00%、10.00%和16.00%,均显著低于对照组(分别为43.59%、74.36%、87.18%和89.74%,均P<0.01);卡维地洛对心肌细胞SOICR的抑制在不同起搏频率下无明显差异(P>0.05)。酚妥拉明、美托洛尔和硝苯地平组细胞与对照组细胞比较,SOICR发生率无差异(均P>0.05)。(3)起搏细胞钙瞬变振幅的比较,各组间相比未见明显差异(P>0.05);咖啡因峰值估测钙库钙总量的比较,各组间也无明显差异(P>0.05)。结论:卡维地洛可明显抑制起搏心肌细胞SOICR的发生,其作用机制可能是直接抑制RyR2的自发性开放而非源于对α1、β1受体和L型钙通道的阻滞作用。AIM： To explore the effect of carvedilol on store overload-induced Ca^2＋ release..（SOICR） in pacing cardiomyocytes. METHODS： Single rat cardiomyocyte with rapid pacing was perfused with isoprenaline and caffeine to induce calcium overload. Spontaneous calcium releases through sarcoplamic reticulum calcium release channel （ryanodine receptor 2, RyR2） were investigated by the method of fluorescence imaging. The cardiomyocytes were divided into control （DMSO） group, carvedilol group, metoprolol group, phentolamine group and nifedipine group. RESULTS ： In control group, the incidence of SOICR in cardiomyocytes was significantly increased under the condition of calcium overload by perfusing with isoprenaline and caffeine in addition to the enhancement of calcium transient. The incidence of SOICR in carvedilol group was significantly lower than that in control group at the pacing frequency of 1 Hz to 4 Hz （ 2. 00%, 6.00%, 10.00% and 16.00% vs43.59%, 74.36%, 87.18% and 89.71%, respectively, P〈0.01）. The inhibitory effect of carvedilol was not significantly different at variant pacing frequency （ P 〉 0.05 ）. The incidences of SOICR in metoprolol group, phentolamine group and nifedipine group had no significant difference compared with control group （ P 〉 0.05）. The amplitude of calcium transient and caffeine peaking value of pacing cardiomyocytes had no significant difference among different groups （ P 〉 0.05）. CONCLUSION： Carvedilol effectively suppresses SOICR in pacing cardiomyocytes due to its direct inhibition on the spontaneous opening of the cardiac RyR2 channel rather than the α1, β1 receptor or L-type calcium channel blockade.

关 键 词：心律失常 卡维地洛 兰尼碱受体2 自发性钙释放 

分 类 号：R541.7[医药卫生—心血管疾病]