低剂量双酚A对雌性大鼠心脏的急性促心律失常作用及其电生理机制

Acute proarrhythmic effect of low dose of bisphenol A on female adult rat and the electrophysiologic mechanisms

目的探讨低剂量双酚A(BPA)对大鼠心脏的促心律失常的作用及其机制。方法将大鼠体外分离的心室肌细胞分成正常对照组、BPA组(10^(-9)mol/L,2×10^(-9)mol/L)、雌二醇(E_(2))组(10^(-9)mol/L,2×10^(-9)mol/L)、BPA+E_(2)组;离体心脏实验分成正常对照组、BPA+E_(2)组、去甲肾上腺(ISO)组和BPA+E_(2)+ISO组,用共聚焦荧光显微镜检测后瞬时,用PowerLab 4/30记录离体心脏心电图。结果雌性大鼠心肌细胞BPA组及E_(2)组的细胞收缩率均高于正常对照组,BPA+E_(2)组的细胞收缩率高于正常对照组、BPA组及E_(2)组,差异有统计学意义(P<0.01)。雄性大鼠心肌细胞BPA组、E_(2)组与正常对照组的细胞收缩率比较,差异无统计学意义(P>0.05)。BPA组及2×10^(-9)mol/L BPA组的心室肌细胞后瞬时百分比均高于正常对照组,差异有统计学意义(P<0.01);E_(2)组的心室肌细胞后瞬时百分比高于正常对照组,差异有统计学意义(P<0.05);2×10^(-9)mol/L E_(2)组的心室肌细胞后瞬时百分比高于正常对照组,差异有统计学意义(P<0.01);BPA+E_(2)组的心室肌细胞后瞬时百分比高于正常对照组、BPA组及E_(2)组,差异有统计学意义(P<0.05)。ISO+BPA+E_(2)组的离体心脏室早频率高于正常对照组、BPA+E_(2)组及ISO组,差异有统计学意义(P<0.05)。结论急性期低剂量的BPA能通过诱导大鼠心室肌细胞产生延迟后除极(DAD),促进心律失常发生,这一作用为雌性性别特异性,低剂量的BPA与生理浓度的E_(2)之间存在着协同作用。

Objective To investigate the female specific acute proarrhythmic effect of low dose of bisphenol A(BPA)on adult rat and the electrophysiologic mechanisms.Methods The isolated ventricular myocytes were divided into normal control group,BPA group(10^(-9)mol/L,2×10^(-9)mol/L),estradiol(E_(2))group(10^(-9)mol/L,2×10^(-9)mol/L)and BPA+E2 group.The isolated heart experiment was divided into normal control group,BPA+E2 group,norepinephrine(ISO)group and BPA+E2+ISO group.The electrocardiogram of the isolated heart was recorded by PowerLab 4/30 immediately after confocal fluorescence microscopy.Results The cell shrinkage rates of female rat cardiomyocytes in BPA and E2 groups were higher than that in normal control group,and that in BPA+E2 group was higher than that in normal control group,BPA group and E2 group,and the differences were statistically significant(P<0.01).There was no statistically significant difference in cell shrinkage rate between BPA and E_(2) groups and normal control group(P>0.05).The transient percentage of ventricular myocytes in BPA group and 2×10^(-9)mol/L BPA group were higher than that in normal control group,and the differences were statistically significant(P<0.01).The transient percentage of ventricular myocytes in E_(2) group was higher than that in normal control group,and the difference was statistically significant(P<0.05).The transient percentage of ventricular myocytes in 2×10^(-9)mol/L E2 group was higher than that in normal control group,and the difference was statistically significant(P<0.01).The transient percentage of ventricular myocytes in BPA+E2 group was higher than that in normal control group,BPA group and E_(2) group,and the differences were statistically significant(P<0.05).The in vitro ventricular premature frequency of ISO+BPA+E_(2) group was higher than that of normal control group,BPA+E_(2) group and ISO group,and the differences were statistically significant(P<0.05).Conclusion Low doses of BPA in acute phase can induce cardiac arrhythmias by inducing delayed after depolarization(DAD)generation in rat ventricular myocytes.This effect is sex-specific in females,and there is a synergistic effect between low doses of BPA and physiological concentration of E_(2).