心肌梗死后β_2肾上腺素受体对心室肌细胞钠钙交换电流的调控作用

目的研究β2受体对心肌梗死(MI)后2~8周心肌细胞钠钙交换电流(INCX)的调控作用。方法雄性健康Wistar大鼠28只,随机分为:正常对照组;MI后2周、4周、8周组。以结扎心脏左前降支方法制作MI模型。正常对照组进行假手术。采用经典的酶分离心肌细胞方法,应用全细胞膜片钳技术记录INCX,观察MI后INCX的变化,予以β2受体激动剂salbutamol、β受体激动剂异丙肾上腺素及不同选择性β受体阻滞剂后INCX的变化。结果MI后8周心肌细胞INCX显著增高(1.07±0.21pA/pFvs0.51±0.12pA/pF,P<0.05)。MI后β2受体激动显著增加心肌细胞INCX(P<0.05),对INCX的调节作用较正常心肌细胞强。MI后选择性β2受体阻滞剂ICI118,551对β受体激动引发的心肌细胞INCX升高的抑制程度增高;选择性β1受体阻滞剂阿替洛尔对上述作用的抑制程度下降;非选择性β受体阻滞剂普萘洛尔对β受体激动引发的正常和MI后心肌细胞上述离子通道电流升高均能明显抑制。结论MI后β2受体对心肌细胞INCX的调节作用增强,提示MI后β2受体在恶性心律失常发生机制中的地位可能提高。

The regulation effects of β2-adrenergic receptor on INCX in myocytes from infarcted heart

Objective To investigate the regulation effects of β_2-adrenergic receptor(β_2-AR) on I_ NCX in myocytes from infarcted heart. Methods Twenty-eight adult Wistar rats were divided into four groups at random: the control group, the two weeks, four weeks and eight weeks post-MI groups. The chest of rats were opened and a ligature was placed around the left anterior descending coronary artery. Rats in control group were sham-operated without the coronary artery ligation. After the operation, rats were fed for two, four or eight weeks respectively. Myocytes were enzymatically disassociated by Langedorff perfusion. The whole cell-patch clamp recording technique was used to record I_ NCX in specific pipette solution and superfusion according to specific holding potential and command potential program. Results I_ NCX in ventricular myocytes from the border zone of infarcted heart increased significantly at eight weeks after MI(1.07±0.21 pA/pF vs 0.51±0.12 pA/pF, P<0.05).β_2-AR agonist increased I_ NCX more strongly in myocytes from post-MI heart than in controls. β_2-AR antagonist attenuated the rise of I_ NCX induced by β-AR agonist more strongly in myocytes from post-MI heart than in controls, whereas β_1-AR antagonist was opposite to β_2-AR antagonist. Conclusion The regulation effects of β_2-AR on I_ NCX in myocytes are stronger after MI. It suggests that β_2-AR has closer relationship with the genesis of malignant arrhythmia after MI.