YE Qiang, ZHA Kelan, YANG Ruixue, et al. Effect and mechanism of sacubitril on ventricular arrhythmias in rats with heart failure after myocardial infarction. [J]. Journal of Southwest Medical University 46(2):135-140(2023)
DOI:
YE Qiang, ZHA Kelan, YANG Ruixue, et al. Effect and mechanism of sacubitril on ventricular arrhythmias in rats with heart failure after myocardial infarction. [J]. Journal of Southwest Medical University 46(2):135-140(2023) DOI: 10.3969/j.issn.2096-3351.2023.02.010.
Effect and mechanism of sacubitril on ventricular arrhythmias in rats with heart failure after myocardial infarction
Objective To investigate the effect of angiotensin receptor/neprilysin inhibitor (ARNI) on ventricular arrhythmias in rats with heart failure (HF) after myocardial infarction and its possible mechanism. Methods SD rats with heart failure after myocardial infarction were established by ligation of left anterior descending coronary artery,and then divided into heart failure group (HF group), angiotensin receptor/neprilysin inhibitor (ARNI) (HF+ARNI group) (68mg/kg/d,intragastric),valsartan group (HF+ARB group) (30mg/ kg/d,intragastric),and mitochondrial Ca2+ uniporter protein (MCU) inhibitor-ruthenium red group (HF+RR group) (2mg/kg/d,intraperitoneal injection). The sham operation group (Sham group) was also established. Continuous drug intervention lasted for 4 weeks. Echocardiography was performed before and after drug intervention. The induction rate of ventricular arrhythmia was detected by Burst stimulation. HE staining was used to observe the histopathological changes of rat heart. The expression of MCU in rat myocardium was detected by Western blot. Results Compared with the Sham group,the HF group had cardiac structural remodeling and significantly decreased cardiac function ((P < 0.05). Compared with HF group and HF+RR group,the cardiac structural remodeling and cardiac function of rats in HF + ARNI group were significantly improved (P < 0.05). Compared with HF + ARB group,the cardiac structural remodeling of rats in HF + ARNI group was significantly improved (P < 0.05),but the cardiac function of rats in HF + ARNI group was not significantly improved (P > 0.05). Compared with HF group and HF+RR group,the induction rate of ventricular arrhythmia in HF+ARNI group was significantly decreased when the voltage was 6V and 12V with the Burst stimulation (P < 0.05). Compared with HF +ARB 0.05). Western blot results showed that compared with Sham group,the expression level of MCU protein in myocardium of rats in HF group was significantly increased (P < 0.05). Compared with HF group,the expression of MCU protein in HF+ARNI group,HF+RR group and HF + ARB group was decreased (P < 0.05). Compared with HF+ARB group,the expression of myocardial MCU in HF+ARNI group was significantly decreased ((P < 0.05). Compared with HF+ARNI group,the expression of myocardial MCU in HF+ RR group was significantly decreased (P < 0.05). Conclusion ARNI could significantly reduce the induction rate of ventricular arrhythmias in rats with heart failure after myocardial infarction,which might be through improving cardiac function and structural remodeling,and down-regulating the expression of MCU.
关键词
沙库巴曲缬沙坦心肌梗死心力衰竭室性心律失常线粒体钙单向转运体
Keywords
Sacubitril/valsartanMyocardial infarctionHeart failureVentricular arrhythmiasMitochondrial Ca2+ uniporter protein
Effect of Empagliflozin on ventricular arrhythmias in rats with myocardial infarction by dose-dependent regulation of autophagy
Correlation analysis of high sensitive C-reactive protein and cardiac function in patients with chronic heart failure complicated by atrial fibrillation
Related Author
叶
强
丁艳玲
敬玉玲
李
涛
LIUHUO Wusha
TANG Chao
Related Institution
Department of Cardiology,The Affiliated Hospital of Southwest Medical University
Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province,Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease,Institute of Cardiovascular Research,Southwest Medical University
Department of Cardiovascular Medicine,the Affiliated TCM Hospital of College of Southwest Medical University