Visfatin对离体大鼠心肌的负性肌力作用及机制研究

A Negative Inotropic Role of Visfatin on the Isolated Rat Heart and the Underlying Mechanism

目的观察内脏脂肪素(visfatin)对离体灌流大鼠心肌的作用,探讨其离子通道机制。方法应用Langendorff心脏灌流装置观察25、50、100、200 nmol·L^(-1) visfatin灌流15 min对离体大鼠心脏心率(HR)、冠脉流量(CF)和心功能指标的影响,应用全细胞膜片钳技术观察50、100、200 nmol·L^(-1) visfatin灌流5 min对单个大鼠心室肌细胞钠钙交换电流(INa/Ca)和L型钙通道电流(ICa,L)的影响。结果 50、100和200 nmol·L^(-1) visfatin灌流15min后,离体灌流大鼠心脏左心室收缩压(LVSP)、左室内压最大上升和下降速率(±dp/dp)显著低于对照组(P<0.01)。50、100和200 nmol·L^(-1) visfatin灌流5 min后,单个大鼠心室肌细胞内向INa/Ca显著增大;50、100和200 nmol·L^(-1)visfatin灌流5 min后单个大鼠心室肌细胞ICa,L明显降低。结论 visfatin对离体大鼠心脏发挥负性肌力作用,其机制可能是由于visfatin浓度依赖性的增大单个大鼠心室肌细胞内向INa/Ca,降低ICa,L。

Objective To investigate the effect of visfatin on the function of the isolated rat hearts and to clarify its ion channel mechanisms. Methods Using Langendorff apparatus the heart rate（HR）,coronary flow（CF）and functional parameters of the isolated rat hearts were measured after perfused with 25,50,100 and 200 nmol·L^（-1） visfatin for 15 min. Using whole-cell voltage-clamp technique,sodium-calcium exchange current（INa/Ca）and L-type calcium channel current（ICa,L）of individual rat ventricular myocytes were measured after perfused with50,100 and 200 nmol·L^（-1） visfatin for 5 min. Results After perfusion with 50, 100 and 200 nmol·L^（-1） visfatin for15 min,left ventricular systolic pressure（LVSP）,the maximum rate of increase or decrease in left ventricular pressure（±dp/dp）of the isolated perfused rat hearts was significantly lower than that of the control group.Treatment with 50,100 and 200 nmol·L^（-1） visfatin for 5 min significantly increased inward INa/Caof individual rat ventricular myocytes. Perfusion with 50,100 and 200 nmol·L^（-1） visfatin for 5 min,significantly decreased ICa,Lvs.the control group. Conclusion The results showed that visfatin played a negative inotropic role on the isolated rat heart,which may result from increased inward INa/Caand decreased ICa,Lof individual rat ventricular myocytes.