重组人脑钠肽对兔缺血再灌注后心室肌细胞L-钙离子通道电流的影响

Influence of recombinant human brain natriuretic peptide on current of ventricular myocyte L-type calcium channels in rabbits after myocardial ischemia-reperfusion

目的研究重组人脑钠肽(rhBNP)对缺血再灌注后心室肌细胞L-钙通道电流(ICa-L)的影响,并探讨其细胞学离子机制。方法 45只新西兰大耳白兔随机分为缺血再灌注动物模型组(I-R组,n=15)、rhBNP治疗组(n=15)和假手术组(n=15)。采用酶解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ICa-L。结果①心律失常发生率:与I-R组比较,rhBNP组兔室速、室颤发生率及持续时间明显下降,而且其心律失常的评分也明显低于I-R组[(2.6±0.7)vs.(3.6±0.8),P<0.05];②电流密度峰值:I-R组、对照组、rhBNP组ICa-L电流密度峰值(0mV)逐渐升高,分别为(-4.34±0.92)pA/pF、(-3.42±0.76)pA/pF、(-3.13±1.22)pA/pF。结论 rhBNP可降低心肌缺血再灌注期间心律失常的发生率,心肌缺血再灌注后ICa-L明显增高,rhBNP可使ICa-L下调,逆转电重构。

Objective To establish rabbit model of myocardial ischemia/reperfusion,study the influence of recombinant human brain natriuretic peptide（rhBNP） on current of ventricular myocyte L-type calcium channels（I Ca-L）,and explore the ionic mechanism.Methods New Zealand rabbits（n=45）were randomly divided into model group（n =15）,treatment group（n=15）and sham-operation group（n=16）.Single ventricular myocytes were isolated by using enzymolysis method from ventricular epicardium in ischemia area.The current of I Ca-L was recorded by using whole-cell patch clamp technique.Results ① Incidence of arrhythmia：the incidence and duration of ventricular tachycardia and ventricular fibrillation,and scores of arrhythmia all decreased significantly in treatment group compared with model group [（2.6 ± 0.7）vs.（3.6 ± 0.8）,P〈0.05].② The peak value of I Ca-L current density（0 mV）increased gradually in model group,control group and treatment groups [（-4.34 ± 0.92）pA/pF,（-3.42 ± 0.76）pA/pF and（-3.13 ± 1.22）pA/pF].Conclusion During the stage of myocardial ischemia/reperfusion,rhBNP can reduce the incidence of arrhythmia.The current of I Ca-L increases significantly after myocardial ischemia/reperfusion,while rhBNP can down-regulate increased I Ca-L current and reverse electrical remodeling.