Mechanism of melatonin in controlling autophagy to relieve arrhythmia in rats with myocardial infarction
Li Jia
Di Yunfeng
Zhou Tao
Xu Min
Li Xuelian
Jiang Xia
Li Decai
Abstract：Objective To discuss the effect and relative mechanism of melatonin in relieve arrhythmia in rats with myocardial infarction(MI).Methods MI model was established by using ligation of left anterior descending coronary artery,and then successfully modeled rats were randomly divided into model group,low-dose melatonin group,mid-dose melatonin group,high-dose melatonin group and high-dose melatonin+mTOR inhibitor group(each n=9).The indexes of left ventricular anterior wall thickness at end diastole(LVAWTd),left ventricular end-diastolic inner diameter(LVEDd),left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESd)and left ventricular short-axis anterior wall thickness at end diastole(LVSAWTd)were detected by using echocardiography.The threshold of ventricular fibrillation was detected by using cardiac physiological electrical stimulation,and pathological changes of myocardial tissue were observed by using HE and Masson staining.The number of apoptotic cardiomyocytes was observed by using TUNEL staining,and expressions of autophagy-related proteins in myocardial tissue,LC3,Beclin1,ATG7,and P62,were detected by using Western blotting assay.Results In model group,LVSAWTd,LVAWTd and LVEF decreased significantly,LVESd and LVEDd increased significantly(P<0.001),and collagen volume fraction(CVF)and number of apoptotic cardiomyocytes increased significantly(P<0.001).Compared with model group,LVSAWTd,LVAWTd and LVEF increased significantly,LVESd and LVEDd decreased significantly(P<0.05),and CVF and number of apoptotic cardiomyocytes decreased significantly in low-dose melatonin group,mid-dose melatonin group and high-dose melatonin group(P<0.05).The ratio of LC 3II to LC 3I(LC 3II/LC 3I)and expressions of Beclin1 and ATG7 increased significantly,and P62 expression decreased significantly in model group(P<0.001).Compared with model group,LC 3II/LC 3I and expressions of Beclin1 and ATG7 decreased significantly,and P62 expression increased significantly in low-dose melatonin group,mid-dose melatonin group and high-dose melatonin group(P<0.05).The curative effect of melatonin disappeared and autophagy ability resumed in high-dose melatonin+mTOR inhibitor group.Conclusion Melatonin can improve heart function and prevent arrhythmia in MI rats,and the mechanism may be related to controlling autophagy.
Keywords：Myocardial infarctionMelatoninAutophagyArrhythmia
Publication Date：2023-09-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1115-1118,1123 )