目的:探讨伊伐布雷定(IVA)对心肌梗死大鼠心肌细胞Notch和 NF-κB信号通路的影响。方法:采用结扎冠状动脉左前降支建立心肌梗死模型,将存活大鼠随机分为模型组(MI组,n=8)和治疗组(IVA组,n=8)。以相同部位穿线但不结扎冠状动脉左前降支的大鼠作为对照组(CON组,n=8)。 IVA给药28 d。检测所有大鼠血流动力学和心功能指标:心率(HR)、收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)和左室内压最大上升和下降速率(±dp/dt)；左室重量指数、左室截面直径和心肌梗死面积；RT-PCR检测大鼠心肌细胞Notch信号通路成分mRNA的表达水平(Notch-1、Dll-4、Hes-1)；Western-blot检测DICD-1蛋白和P65蛋白表达水平。组间比较采用单因素方差分析,两两比较采用 SNK法。结果:MI组SBP、 DBP、MAP、LASP、LVEDP和±dp/dt均低于对照组(P＜0.05)；而IVA上述指标均高于MI组(P＜0.05)。MI组左室重量指数和左室截面直径明显大于对照组(P＜0.05),但小于IVA组(P＜0.05)。MI组Notch-1 mRNA表达水平明显高于对照组(P＜0.05),但低于IVA组(P＜0.05)。3组Dll-4和Hes-1 mRNA表达水平的比较差异无统计学意义(P＞0.05)。MI组心肌细胞NICD-1蛋白和P65蛋白表达水平明显高于CON组(P＜0.05),但是低于IVA组(P＜0.05)。结论:IVA可能通过Notch和 NF-κB信号通路发挥改善心肌梗死大鼠心功能和抑制心室重构的作用。
Objective: To investigate the effects of ivabradine on Notch and NF-kappa B signaling pathway in myocardial cells of rats with myocardial infarction. Methods: The model of myocardial infarction was established by ligating the left anterior descending coronary artery. The surviving rats were randomly divided into model group (MI group, n=8) and treatment group (IVA group, n=8). Rats with the same location but without ligation of the left anterior descending coronary artery were used as control group (CON group, n=8). IVA was administered for 28 d. Hemodynamic and cardiac function indexes of all rats were measured:heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rate of increase and decrease of left ventricular internal pressure (+dp/dt); left ventricular mass index, left ventricular cross-sectional diameter and infarct area; The expression of Notch signaling pathway components (Notch-1, Dll-4, Hes-1) in rat cardiomyocytes was detected by PT-PCR, and the expression of DICD-1 and P65 protein was detected by western-blot. One-way ANOVA was used for comparison between groups, and SNK was used for comparison between groups. Results: SBP, DBP, MAP, LASP, LVEDP and (+dp/dt) in MI group were lower than those in control group (P<0.05), while IVA was higher than those in MI group (P<0.05). Left ventricular mass index and left ventricular sectional diameter in MI group were significantly higher than those in control group (P<0.05), but lower than those in IVA group (P<0.05). The expression of Notch-1 in MI group was significantly higher than that in control group (P<0.05), but lower than that in IVA group (P<0.05). There was no significant difference in the expression of Dll-4 and Hes-1 between the three groups (P>0.05). The expression levels of NICD-1 and P 65 in MI group were significantly higher than those in CON group (P<0.05), but lower than those in IVA group (P<0.05). Conclusion: IVA may improve cardiac function and inhibit ventricular remodeling in rats with myocardial infarction through Notch and NF-kappa B signaling pathways.