Effects of Artesunate on Autophagy and Apoptosis in Rats with Myocardial Ischemia-reperfusion Injury through Regulation of the LKB1/AMPK Signaling Pathway
ZHANG Zhiling
DI Xueqin
MA Xiaoru
CHEN Ling
MA Shuyi
ZANG Yanwei
TIAN Xin
Abstract：Objective:To investigate the effects of artesunate on autophagy and apoptosis in rats with myocardial ischemia-reperfusion(I/R)injury by regulating the liver kinase B1(LKB1)/5'-AMP activated protein kinase(AMPK)signaling pathway.Methods:A rat myocardial I/R injury model was established using the left anterior descending coronary artery ligation method.The model group was randomly divided into three groups:the model group,the artesunate(150 mg/kg)group,and the artesunate(150 mg/kg)+radicicol(AMPK inhibitor,20 mg/kg)group,with 10 rats in each group.Additionally,10 rats were randomly assigned to a sham operation group without ligating the coronary artery.After grouping and treatment with artesunate and radicicol,ultrasound was used to assess cardiac function in rats in each group,and cardiac function indicators such as heart rate(HR),left ventricular end-systolic volume(LVESV),left ventricular wall thickness(LVWT),and left ventricular ejection fraction(LVEF)were compared.Terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)staining was applied to detect myocardial cell apoptosis in rats of each group.Transmission electron microscopy was applied to observe the ultrastructure of myocardial cells in rats from each group,and the number of autophagosomes within the cells was compared.An enzyme-linked immunosorbent assay(ELISA)kit was used to measure the levels of pro-inflammatory factors,such as tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),in the serum and myocardial tissue of rats in each group.Western blot was applied to detect the expression of apoptosis-related proteins(Bcl-2,Bax),autophagy-related proteins(LC3,p62),and LKB1/AMPK pathway-related proteins in the myocardial tissue of rats in each group.Results:Compared with the sham surgery group,the myocardial cell ultrastructure of rats in the model group showed significant damage;heart rate,LVWT,LVEF,the expression of Bcl-2 protein,and p-LKB1/LKB1 and p-AMPK/AMPK ratios in myocardial tissue were obviously reduced(P＜0.05);LVESV,myocardial apoptosis index,number of autophagosomes,levels of TNF-α and IL-1β in serum and myocardial tissue,expression of Bax and P62 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio in myocardial tissue were significantly increased(P＜0.05).Compared with the model group,the myocardial cell ultrastructure damage in the artesunate group was reduced,the heart rate,LVWT,LVEF,number of autophagosomes,the expression of Bcl-2 and p62 proteins,LC3-Ⅱ/LC3-Ⅰ ratio,p-LKB1/LKB1,and p-AMPK/AMPK in myocardial tissue increased(P＜0.05),the LVESV,myocardial apoptosis index,the levels of TNF-α and IL-1β in serum and myocardial tissue,and the expression of Bax protein in myocardial tissue decreased(P＜0.05).Compared with the artesunate group,the myocardial cell ultrastructure damage in the artesunate+radicicol group was aggravated;heart rate,LVWT,LVEF,number of autophagosomes,expression of Bcl-2 and p62 proteins,LC3-Ⅱ/LC3-Ⅰ ratio,p-LKB1/LKB1 ratio,and p-AMPK/AMPK ratio in myocardial tissue decreased(P＜0.05);meanwhile,LVESV,myocardial apoptosis index,serum and myocardial levels of TNF-α and IL-1β,and myocardial expression of Bax protein increased(P＜0.05).Conclusion:Artesunate can inhibit inflammation and enhance autophagy by activating LKB1/AMPK signaling,thereby reducing myocardial cell apoptosis and damage in rats with myocardial I/R injury,and ultimately improving their cardiac function.
Keywords：myocardial ischemia-reperfusion injuryartesunateliver kinase B15'-AMP activated protein kinaseautophagyapoptosisexperimental study
Publication Date：2025-12-10
Online Publishing Date：2025-12-19(First online date of this platform, not the publication date of the document)
Pages：7( 3570-3576 )