The Effect of Ezetimibe on Cardiac Function and PI3K/AKT/GSK3 β Signaling Pathway after Acute Myocardial Infarction in Hyperlipidemic Rats
[Objective]To investigate the effects of ezetimibe on cardiac function and the phosphatidylinosi-tol 3-kinase/protein kinase B/glycogen synthase kinase 3β(PI3K/AKT/GSK3β)pathway after acute myocardi-al infarction in hyperlipidemic rats.[Methods]Fifty successfully modeled hyperlipidemic rats were randomly divided into a high-fat sham surgery group(n=16),a high-fat AMI group(n=17),and an ezetimibe group(n=17).Eight rats were randomly selected and fed with regular feed(normal control group).The high-fat AMI group and ezetimibe group rats underwent coronary artery ligation surgery to establish AMI models(the high-fat sham surgery group only had suture without ligation).48 hours after surgery,there were 10,9,and 9 surviving rats in the high-fat sham surgery group,high-fat AMI group,and ezetimibe group,respectively.We compared the levels of left ventricular end systolic volume(LVESV),left ventricular end diastolic diame-ter(LVEDV),and left ventricular ejection fraction(LVEF)in each group of rats after gastric lavage,ob-served the pathological changes in rat myocardial tissue,compared the apoptosis index(AI)of myocardial cells in each group,and compared the changes in PI3K,p-PI3K,AKT,p-AKT,GSK3β,and p-GSK3β protein lev-els in myocardial tissue.[Results]Compared with the normal control group and high-fat sham surgery group,the levels of LVEDV and LVESV increased(P＜0.05)and LVEF decreased in the high-fat AMI group and ezetimibe group rats(P＜0.05);The LVEDV and LVESV levels in the ezetimibe group were lower than those in the high-fat AMI group(P＜0.05),and the LVEF level was higher than that in the high-fat AMI group(P＜0.05).Compared with the high-fat AMI group rats,the pathological changes in the myocardial tissue of the ezetimibe group rats were improved.Compared with the normal control group and the high-fat sham surgery group,the AI levels of myocardial cells in the high-fat AMI group and the ezetimibe group were increased(P＜0.05);The AI level of myocardial cells in the ezetimibe group was lower than that in the high-fat AMI group(P＜0.05).Compared with the normal control group and high-fat sham surgery group,the levels of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3β in the myocardial tissue of rats in the high-fat AMI group and ezetimibe group were all reduced(P＜0.05);The levels of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3β in the myocardial tissue of rats in the ezetimibe group were higher than those in the high-fat AMI group(P＜0.05).[Conclusion]Ezetimibe may inhibit myocardial cell apoptosis by promoting the activa-tion of the PI3K/AKT/GSK3β pathway,and exert a protective effect on cardiac function in hyperlipidemic rats after AMI.
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