依折麦布对高脂血症大鼠急性心肌梗死后心功能及PI3K/AKT/GSK3β信号通路的影响

doi:10.3969/j.issn.1671-7171.2024.08.013

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摘要【目的】探讨依折麦布对高脂血症大鼠急性心肌梗死(AMI)后心功能及磷脂肌醇3-激酶/蛋白激酶B/糖原合成酶激酶3β(PI3K/AKT/GSK3β)通路的影响。【方法】将50只建模成功的高脂血症大鼠随机分为高脂假手术组(n=16)、高脂AMI组(n=17)、依折麦布组(n=17),随机选取8只大鼠以普通饲料饲养(正常对照组)。高脂AMI组、依折麦布组大鼠行冠脉结扎手术建立AMI模型(高脂假手术组只穿线不结扎),术后48 h,高脂假手术组、高脂AMI组、依折麦布组存活大鼠分别为10只、9只、9只。比较灌胃结束后各组大鼠左室收缩末期容积(LVESV)、左室舒张末期内径(LVEDV)、左室射血分数(LVEF),观察大鼠心肌组织病理形态学变化,比较各组大鼠心肌细胞凋亡指数(AI),以及心肌组织中PI3K、p-PI3K、AKT、p-AKT、GSK3β、p-GSK3β蛋白水平变化。【结果】与正常对照组、高脂假手术组比较,高脂AMI组、依折麦布组大鼠LVEDV、LVESV水平升高(P<0.05),LVEF水平降低(P<0.05);依折麦布组大鼠LVEDV、LVESV水平低于高脂AMI组(P<0.05),LVEF水平高于高脂AMI组(P<0.05)。与高脂AMI组大鼠比较,依折麦布组大鼠上述心肌组织病理学变化有所改善。与正常对照组、高脂假手术组比较,高脂AMI组、依折麦布组心肌细胞AI均升高(P<0.05);依折麦布组大鼠心肌细胞AI水平低于高脂AMI组(P<0.05)。与正常对照组、高脂假手术组比较,高脂AMI组、依折麦布组大鼠心肌组织p-PI3K/PI3K、p-AKT/AKT、p-GSK3β/GSK3β水平均降低(P<0.05);依折麦布组大鼠心肌组织p-PI3K/PI3K、p-AKT/AKT、p-GSK3β/GSK3β水平高于高脂AMI组(P<0.05)。【结论】依折麦布可能通过促进PI3K/AKT/GSK3β通路活化抑制心肌细胞凋亡,对高脂血症大鼠AMI后心功能发挥保护作用。

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	延云鹏
	王淼

关键词 ：高脂血症/并发症, 心肌梗死/并发症, 急性病, 依折麦布, 疾病模型,动物, 大鼠

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.

Key words： Hyperlipidemias/CO Myocardial Infarction/CO Acute Disease Ezetimibe Disease Models, Animal Rats

收稿日期: 2022-06-20

中图分类号:

R589.21

引用本文:

延云鹏, 王淼. 依折麦布对高脂血症大鼠急性心肌梗死后心功能及PI3K/AKT/GSK3β信号通路的影响[J]. 医学临床研究, 2024, 41(8): 1164-1167.
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. JOURNAL OF CLINICAL RESEARCH, 2024, 41(8): 1164-1167.

链接本文:

http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2024.08.013 或 http://journal07.magtech.org.cn/yxlcyj/CN/Y2024/V41/I8/1164

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