摘要
目的:探讨人类真核翻译延长因子(EEF1A1)对急性心肌梗死(AMI)模型大鼠心肌细胞凋亡及Notch/蛋白激酶B(AKT)转导途径的影响。方法:将30只SD雄性大鼠随机分为假手术组、模型组、干预组,每组10只,模型组、干预组于冠状动脉左前降支结扎建立AMI大鼠模型,对照组仅手术穿线处理不结扎。建模后24 h干预组于心肌梗死区原位注射EEF1A1腺病毒,模型组、对照组注射等量生理盐水。干预72 h后,心脏彩超测定大鼠心功能,采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色法评估心肌细胞凋亡,2,3,5-氯化三苯基四氮唑(TCC)染色法评估心肌梗死面积,采用实时定量聚合酶链式反应(RT-PCR)法测定EEF1A1 mRNA表达量,蛋白免疫印迹法(Western Blot)检测心肌组织EEF1A1蛋白以及Notch/AKT信号通路相关蛋白表达情况。结果:干预前,模型组、干预组左室射血分数(LVEF)明显低于假手术组(P<0.05),而左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)明显高于假手术组(P<0.05);干预后3 d后,干预组LVEDD、LVESD明显降低,而LVEF明显增加,模型组LVEDD、LVESD明显增加,而LVEF明显降低,差异均有统计学意义(P<0.05)。干预组心肌组织EEF1A1蛋白及mRNA表达水平高于假手术组、模型组(P<0.05),而模型组心肌组织EEF1A1蛋白及mRNA表达水平高于假手术组(P<0.05)。干预组心肌梗死面积小于模型组(P<0.05)。干预组心肌细胞凋亡率明显高于假手术组(P<0.05),明显低于模型组(P<0.05)。干预组Notch1、Hes1、磷酸化AKT(p-AKT)/AKT相关蛋白表达明显高于模型组、假手术组,模型组Notch1、Hes1、p-AKT/AKT相关蛋白表达均明显高于假手术组(P<0.05)。结论:EEF1A1可抑制AMI大鼠心肌细胞损伤、凋亡,缩小心肌梗死面积,改善心脏功能,其作用机制可能与上调Notch/AKT转导途径有关。
Objective:To explore the effect of homo sapiens eukaryotic translation elongation factor 1 alpha 1(EEF1A1) on myocardial cell apoptosis and Notch/protein kinase B(AKT) transduction pathway in acute myocardial infarction(AMI) rats model.Methods:Thirty male SD rats were randomly divided into sham operation group,model group,and intervention group,with 10 rats in each group.The rats in model group and intervention group AMI rat model,established by ligating the left anterior descending coronary artery,while the control group only underwent surgical threading without ligation.Twenty-four hours after establishment,the rats in intervention group were injected with EEF1A1 adenovirus in situ in the myocardial infarction area,and the rats in model group and control group were injected with the same volume of normal saline.After 72 hours of intervention,the cardiao function was measured by color Doppler ultrasound,the apoptosis of cardiao myocytes was evaluated by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) staining method,the infarct area was evaluated by 2,3,5-triphenyltetrazolium chloride(TCC) staining method,the expression of EEF1A1 mRNA was measured by real-time quantitative PCR method,and the expression of EEF1A1 protein and Notch/AKT signal pathway related protein in myocardial tissue was detected by Western Blot.Results:Before intervention,left ventricular ejection fraction(LVEF) in the model group and intervention group was significantly lower than that in the sham operation group,while left ventricular end-diastolic dimension(LVEDD) and left ventricular end-systolic diameter(LVESD) were significantly higher than those in sham operation group(P<0.05).After 3 days of intervention,LVEDD and LVESD in intervention group significantly decreased,while LVEF significantly increased,and LVEDD and LVESD in model group significantly increased,while LVEF significantly decreased,and the differences were statistically significant(P<0.05).The expression levels of myocardial EEF1A1 protein and mRNA in
作者
朱涛
张为民
阿不都乃比·麦麦提艾力
刘正
艾克热木·吐尔逊
霍强
ZHU Tao;ZHANG Weimin;Abe Dunabi·Mai Mai Ti Ai Li;LIU Zheng;Ai Ke Re Mu·Tu Er Xun;HUO Qiang(The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang,China)
出处
《中西医结合心脑血管病杂志》
2024年第19期3519-3523,共5页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金项目(No.82060907)。
关键词
急性心肌梗死
人类真核翻译延长因子
细胞凋亡
心脏功能
Notch/AKT转导途径
实验研究
acute myocardial infarction
eukaryotic translation elongation factor 1 alpha1
cell apoptosis
cardiac function
Notch/protein kinase B transduction pathway
experimental study