重组人脑钠尿肽对兔缺血/再灌注后心室肌细胞钠离子通道电流的影响

目的研究重组人脑钠尿肽（rhBNP）对兔在体缺血/再灌注（I/R）后心室肌细胞钠离子通道电流（INa）的影响，探讨rhBNP拮抗再灌注心律失常的细胞学离子机制。方法新西兰大耳白兔45只随机分为3组（n＝15）：I/R损伤组（I/R组，缺血30min后再灌注120min）；rhBNP治疗组[rhBNP组，再灌注后经动物耳缘静脉注射rhBNP 0.06μg/（kg·min）]；假手术对照组（CON组，只开胸不结扎血管）。采用酶解的方法分离缺血部位心室肌外膜单个心室肌细胞，应用全细胞膜片钳技术记录INa。结果 CON组、I/R组、rhBNP组INa密度峰值（-30mV）分别为（-42.78±5.48，n＝16），（-22.46±5.32， n＝12），（-37.82±5.45，n＝15）pA/pF，I/R组较CON组明显下降（P＜0.01），rhBNP组较I/R组明显升高（P＜0.01）。结论 I/R后心肌INa明显下降，给予rhBNP可使下降的INa上调，提示rhBNP可减轻或逆转这种电重构。

Effects of rhBNP on sodium current in isolated ventricular myocytes from ischemia/reperfusion myocardium of rabbit

Objective To investigate the effects of recombinant human brain natriuretic peptide （rhBNP） on sodium current （INa） in left ventricular myocytes of rabbit heart undergoing ischemia/reperfusion（I/R）, so as to explore the cellular （ionic） basis of rhBNP treatment for antiarrhythmia. Methods Forty-five rabbits were randomly divided into three groups （n=15）： ischemic/reperfusion （I/R） group, rhBNP intervention （rhBNP） group and sham-operation control （CON） group. Anesthetized rabbits were subjected to 30min ischemia by ligation of the left anterior descending coronary artery and 120min reperfusion. rhBNP group was injected with rhBNP at a dose of 0.06μg/（kg·min） via ear-vein. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I/R, rhBNP groups and the same anatomy region in CON group. Whole cell patch clamp technique was used to record INa. Results The peak INa density （at –30mV） was significantly decreased in I/R group [（–22.46±5.32）pA/pF, n=12] compared with CON group [（–42.78±5.48）pA/pF, n=16; P〈0.01], while it was significantly increased in rhBNP group[（-37.82±5.45）pA/pF, n=15] compared with I/R group（P〈0.01）. Conclusion Ischemia/reperfusion induces significant down-regulation of INa, and pretreatment with rhBNP could attenuate these changes, prevent and reverse this electrical remodeling.