目的:观察荭草苷通过Notch通路对心律失常大鼠的改善作用及对心电图(ECG)的影响。方法:采用舌下注射乌头碱方式建立心律失常大鼠模型,随机分为模型组、荭草苷低剂量组(0.75 mg·kg-1)、荭草苷中剂量组(1.5 mg·kg-1)、荭草苷高剂量组(3 mg·kg-1),另设对照组。干预后监测ECG,比较心率(HR)、Q-T间期、P-R间期、QRS波群时间及室性早搏(PVC)、室性心动过速(VT)、心室颤动(VF)发生时间;HE染色观察心肌组织病理学变化;TUNEL染色观察心肌细胞凋亡情况;比较心肌组织Notch1、Notch受体胞内区域(NICD)、发状分裂相关增强子-1(Hes1)mRNA和蛋白表达情况。结果:与对照组比较,模型组HR加快,Q-T间期、P-R间期延长,QRS波群增宽,心肌细胞凋亡率升高,心肌组织Notch1、NICD、Hes1 mRNA及蛋白表达降低(P＜0.05);与模型组比较,荭草苷各剂量组HR减慢,Q-T间期、P-R间期缩短,QRS波群减窄,PVC、VT、VF出现时间延长,心肌细胞凋亡率降低,心肌组织Notch1、NICD、Hes1 mRNA及蛋白表达升高(P＜0.05),其中荭草苷高剂量组治疗效果最明显(P＜0.05)。结论:荭草苷可能通过调控Notch信号通路,防治心律失常。
Objective: To observe the effect of orientin on arrhythmia rats and its influence on electrocardiogram (ECG) through Notch pathway. Methods: A rat model of arrhythmia was established by sublingual injection of aconitine and randomly divided into a model group, low dose of orientin group (0.75 mg·kg-1), middle dose of orientin group (1.5 mg·kg-1), high dose of orientin group (3 mg·kg-1), and a control group. ECG after intervention was monitored, and the heart rate (HR), QT interval, PR interval, QRS complex time, and time of occurrence of premature ventricular contraction (PVC), ventricular tachycardia (VT), and ventricular fibrillation (VF), HE staining was compared to observe the pathological changes of myocardial tissue.TUNEL staining was used to observe the apoptosis of cardiomyocytes.The mRNA and protein expressions of Notch1, Notch intracellular domain (NICD), hairy and enhancer of split 1 (Hes1) in myocardial tissue were compared. Results: Compared with control group, HR were accelerated, QT interval and PR interval were prolonged, QRS complex was widened, the apoptotic rate of cardiomyocytes was increased, mRNA and protein expressions of Notch1, NICD and Hes1 in myocardial tissue were decreased in model group (P<0.05). Compared with the model group, HR slowed down, QT interval, PR interval shortened, QRS complexes narrowed, the appearance time of PVC, VT, VF prolonged, the apoptotic rate of cardiomyocytes decreased,and the expression of Notch1, NICD, Hes1 mRNA and protein in myocardial tissue increased in each dose group (P<0.05). Among which the high dose of orientin group had the most obvious therapeutic effect (P<0.05). Conclusion: Orientin may prevent and treat arrhythmia by regulating Notch signaling pathway.
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