Abstract 【Objective】To investigate the effects of ezetimibe on cardiac function and the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3β(PI3K/AKT/GSK3β) pathway after acute myocardial 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 diameter (LVEDV), and left ventricular ejection fraction (LVEF) in each group of rats after gastric lavage, observed 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 levels 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 activation of the PI3K/AKT/GSK3β pathway, and exert a protective effect on cardiac function in hyperlipidemic rats after AMI.
YAN Yunpeng,WANG Miao. The Effect of Ezetimibe on Cardiac Function and PI3K/AKT/GSK3 β Signaling Pathway after Acute Myocardial Infarction in Hyperlipidemic Rats[J]. JOURNAL OF CLINICAL RESEARCH, 2024, 41(8): 1164-1167.
[1] HOUSTON M, MINICH D, SINATRA S T, et al. Recent science and clinical application of nutrition to coronary heart disease[J].J Am Coll Nutr,2018, 37(3):169-187.
[2] 李建军, 石文娜. 依折麦布联合非诺贝特治疗混合型高脂血症及颈动脉斑块的临床疗效及安全性[J].中国老年学杂志, 2020, 2(40):720-725.
[3] 邰贺, 姜晓琳, 姚思成, 等. 化瘀祛痰方对高脂血症合并急性心肌梗死大鼠心肌过氧化损伤的影响研究[J].现代中西医结合杂志, 2018, 30(10):6-11.
[4] 吴子建, 蔡荣林, 何璐, 等. 针刺“内关”“神门”穴对高脂血症大鼠心肌梗死后室旁核区和血清5-羟色胺含量的影响[J].针刺研究, 2013, 38(6):482-487.
[5] 陈霞. 辛伐他汀联合依折麦布对高脂喂养ApoE-/-小鼠动脉粥样硬化斑块的作用[J].热带医学杂志, 2015, 15(10):1337-1340.
[6] ARORA G, BITTNER V. Chest pain characteristics and gender in the early diagnosis of acute myocardial infarction[J].Curr Cardiol Rep,2015, 17(2):5-16.
[7] 冯海先, 张玉凤, 任小燕, 等. 依折麦布联合瑞舒伐他汀钙治疗2型糖尿病合并冠心病的临床研究[J].中西医结合心脑血管病杂志, 2020, 18(5):97-100.
[8] 李北方, 刘飞, 文传辉, 等. 瑞舒伐他汀联合依折麦布对早发冠心病急性心肌梗死患者血脂和炎症因子的影响[J].中国执业药师, 2019, 16(4):88-90.
[9] TRAXLER D, SPANNBAUER A, EINZINGER P, et al. Early elevation of systemic plasma clusterin after reperfused acute myocardial infarction in a preclinical porcine model of ischemic heart disease[J].Int J Mol Sci,2020, 21(13):4591-4597.
[10] CHEN L, PEI H, LU S J, et al. SPOP suppresses osteosarcoma invasion via PI3K/AKT/NF-κB signaling pathway[J].Eur Rev Med Pharmacol Sci,2018, 22(3):609-615.
[11] HE M, ZHANG Y, XIE F, et al. Role of PI3K/Akt/NF-κB and GSK-3β pathways in the rat model of cardiopulmonary bypass-related lung injury[J].Biomed Pharmacother,2018, 106(77):747-754.
[12] ZHANG B, ZHANG Y F, LI R, et al. MiR-217 inhibits apoptosis of atherosclerotic endothelial cells via the TLR4/PI3K/Akt/NF-κB pathway[J].Eur Rev Med Pharmacol Sci,2020, 24(24):12867-12877.
[13] 王秀珍, 邹伟, 李冀, 等. 基于PI3K/Akt/GSK-3β信号通路探讨稳心丹对MIRI大鼠心肌保护作用的机制研究[J].中医药学报, 2020, 22(10):6-11.
2024, Vol. 41 
