| Objective: In this study,an animal model of heart failure after acute myocardial infarction was prepared by ligating the left anterior descending coronary artery of the rat heart.To investigate whether its effect on ventricular arrhythmia is related to the regulation of the expression of MCU,and to provide a scientific basis for clinical exploration of the mechanism of sacubitril-valsartan in the treatment of ventricular arrhythmia in patients with heart failure.Methods: Forty adult male Sprague-Dawley rats were selected and fed adaptively for one week,and randomly divided into heart failure group(HF group),sham operation group(Sham group),sacubitril-valsartan group(HF+ARNI group),Valsartan group(HF+ARB group),MCU inhibitor-ruthenium red group(HF+RR group).Except for the sham operation group,the other groups were all used the left anterior descending coronary artery ligation to prepare the acute myocardial infarction model.The thorax passes through the anterior descending artery without ligation.One week after the preparation of the rat model of myocardial infarction,echocardiography was used to detect the left ventricular ejection fraction(LVEF),left ventricuar eject shortening(LVFS),left ventricuar ejection fraction(LVFS),and left ventricuar ejection fraction(LVEF)of the rats in each group.Ventricular end-systolic diameter(Left ventricuar end-systolic diameter,LVESD)and left ventricular end-diastolic diameter(Left ventricuar end-diatolic diameter,LVEDD).Then drug intervention was given.The sacubitril-valsartan group(HF+ARNI group)was given daily gavage of sacubitril-valsartan(68 mg/kg/d),and the valsartan group(HF+ARB group)was given daily Valsartan(68 mg/kg/d)was administered by gavage,and the MCU inhibitor group(HF+RR group)was intraperitoneally injected with MCU inhibitor-ruthenium red(RR)(2 mg/kg/d)every day.After 4 weeks of administration,echocardiography was performed again.The induction rate of ventricular arrhythmia in each group was detected by open-chest burst stimulation.After the rats were sacrificed,the heart tissue was collected and stained with hematoxylin-eosin(HE)to observe the histopathological changes of the rats;Western blot was used to detect the expression of MCU in the myocardium of the rats.Results: 1.The results of echocardiography showed that after the myocardial infarction model was prepared for one week,compared with the sham operation group,the LVEF of the other groups decreased significantly(P< 0.05).Considering the successful preparation of the heart failure model after myocardial infarction.After drug intervention,compared with rats in heart failure group,left ventricular ejection fraction(LVEF)increased in sacubitril-valsartan group after sacubitril-valsartan drug treatment(P = 0.018).,increased short-axis fraction shortening(LVFS)(P = 0.022),left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)(P = 0.004),and left ventricular end-systolic volume(LVESV)decreased(P = 0.005).Compared with the sham operation group,the myocardial infarction group had significantly lower LVEF(P = 0.006),significantly lower LVFS(P = 0.004),wider LVESD(P = 0.007),and smaller LVESV(P = 0.010).Compared with the valsartan group,the sacubitril-valsartan group reduced LVEDD(P = 0.023)and LVESD more significantly(P = 0.033).Compared with the heart failure group,there was no significant difference in LVEF,LVFS,LVEDD,LVESD and LVESD in the MCU inhibitor group(P > 0.05).2.The results of HE staining showed that the space between cardiomyocytes and cardiomyocytes of SD rats in the sham operation group was small,the cardiomyocyte envelope was complete,and arranged neatly together,very compact and regular,and the cells were colored uniformly without distortion.In the heart failure group,the myocardial cells were sparsely arranged,the fibers were twisted and broken,the coloring of the cells was uneven,the interstitial edema,and the infiltration of inflammatory cells.The myocardial fibers in the sacubitril-valsartan group and the valsartan group tended to be neatly arranged,the interstitial edema was reduced,and the inflammatory cell infiltration was reduced.3.Induction rate of ventricular arrhythmia: Compared with the heart failure group,under the stimulation of 6v and 60 v Burst,the sacubitril-valsartan group can significantly reduce the induction rate of ventricular arrhythmia in rats(P<0.001);Compared with the sham-operated group,the induction rate of ventricular arrhythmia was significantly increased in the heart failure group under 6v and 60 v Burst stimulation(P<0.001).Compared with the valsartan group,the sacubitril-valsartan group could significantly reduce the induction rate of ventricular arrhythmia in rats under the stimulation of 60 v Burst(P<0.001).There was no statistical difference in the induction rate of ventricular arrhythmia between the heart failure group and the MCU inhibitor group and the valsartan group under 6v and 60 v Burst stimulation.4.MCU expression: Compared with the rats in the sham operation group,the expression level of MCU protein in the myocardium of the rats in the heart failure group was significantly increased(P < 0.001).Compared with the heart failure group,the sacubitril-valsartan group(P < 0.001),the MCU inhibitor group(P < 0.001)and the valsartan group(P = 0.001)all showed a decrease in the expression of MCU protein.Compared with the valsartan group,the expression of myocardial MCU in the sacubitril-valsartan group was decreased(P = 0.015).Compared with the sacubitril-valsartan group,the expression of myocardial MCU in the MCU inhibitor group decreased more significantly(P = 0.006).Conclusion: Sacubitril-valsartan can improve the cardiac function of rats with heart failure after acute myocardial infarction and reduce the occurrence of ventricular arrhythmia induction rate,which may be related to regulating the expression of MCU. |
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