利拉鲁肽调控PI3K/AKT通路对急性心肌梗死大鼠心肌损伤的影响  

Effect of liraglutide on myocardial injury in rats with acute myocardial infarction via regulating PI3K/AKT signaling pathway

作　　者：卢文君 廖奕华 刘昕禹 刘畅 王道豹 王黎 陈芬 龚芳 LU Wenjun;LIAO Yihua;LIU Xinyu;LIU Chang;WANG Daobao;WANG Li;CHEN Fen;GONG Fang(Department of Cardiology,95829th Army Hospital of the Chinese People's Liberation Army,Wuhan Hubei 430012,China;Xi'an Jiaotong University,Xi'an 710000,China;Department of office Clinic,the 95829 thArmy Hospital of tan Chinese People's Liberation Army,Wuhan 430012,Hubei,China;Department of Cardiology,Union Hospital Tongji Medical College Huazhong University of Science and Technology,Wuhan Hubei 430022,China;Department of Cardiology,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Sciences,Xiangyang Hubei 441021,China)

机构地区：[1]中国人民解放军95829部队医院心血管内科,湖北武汉430012 [2]西安交通大学,陕西西安710000 [3]中国人民解放军95829部队医院机关门诊部,湖北武汉430012 [4]华中科技大学同济医学院附属协和医院心内科,湖北武汉430022 [5]湖北文理学院附属襄阳市中心医院心内科,湖北襄阳441021

出　　处：《贵州医科大学学报》2025年第2期247-253,共7页Journal of Guizhou Medical University

基　　金：湖北省自然科学基金(2020CFB765)。

摘　　要：目的探讨利拉鲁肽通过调控磷酸肌醇3激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI3K/AKT)信号通路对急性心肌梗死(acute myocardial infarction,AMI)大鼠心肌损伤的影响。方法从65只大鼠中随机取12只作为假手术组,其余大鼠均采用冠状动脉结扎法构建AMI大鼠模型,造模成功的48只SD大鼠随机分为模型组、利拉鲁肽组(腹腔注射0.6 mg/kg利拉鲁肽)、LY294002组(PI3K抑制剂,腹腔注射1.5 mg/kg LY294002)及利拉鲁肽+LY294002组(腹腔注射利拉鲁肽后注射LY294002),每组12只;造模成功后药物组按照各组给药方式进行处理,假手术组及模型组腹腔注射等量生理盐水,连续注射2周;末次给药后,采用超声心动图检查各组大鼠心功能指标,多导生理仪记录血流动力学指标,HE染色法检测大鼠心肌组织病理学变化,Masson染色观察心肌组织纤维化程度,Western blot检测心肌组织自噬因子及PI3K/AKT信号通路相关蛋白表达。结果与假手术组比较,模型组心功能显著下降,心肌组织受损程度及纤维化程度严重,自噬相关蛋白及PI3K/AKT通路相关蛋白表达显著降低(P<0.05);与模型组比较,利拉鲁肽组大鼠心功能、心肌组织受损程度及纤维化程度得到缓解,自噬相关蛋白及PI3K/AKT通路相关蛋白表达显著升高(P<0.05);与利拉鲁肽组比较,LY2940002组和利拉鲁肽+LY2940002组大鼠心功能显著降低,心肌组织受损程度及纤维化程度严重,自噬相关蛋白及PI3K/AKT通路相关蛋白表达显著降低(P<0.05);与LY2940002组比较,利拉鲁肽+LY2940002组大鼠心功能、心肌组织受损程度及纤维化程度得到缓解,自噬相关蛋白及PI3K/AKT通路相关蛋白表达显著升高(P<0.05)。结论利拉鲁肽调节PI3K/AKT信号通路,可改善AMI大鼠的心肌损伤,保护心功能。Objective To investigate the impact of liraglutide on myocardial injury in rats with acute myocardial infarction(AMI)via regulating the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Twelve out of 65 SD rats were randomly selected as sham operation group,and the remaining rats were treated with coronary artery ligation to construct AMI rat model,among which,48 SD rats successfully established with AMI,further randomly divided into model group,liraglutide group(intraperitoneal injection of 0.6 mg/kg liraglutide),LY294002 group(PI3K inhibitor,intraperitoneal injection of 1.5 mg/kg LY294002),and liraglutide+LY294002 group(intraperitoneal injection of LY294002 after intraperitoneal injection of liraglutide).There were 12 rats with AMI in each group.Sham operation and model groups were intraperitoneally injected with the same amount of normal saline.The treatment lasted for two continuous weeks.After the last administration,echocardiography was used to check rat heart function indexes,and multi-channel physiometer was used to record rat hemodynamic indicators.HE staining was applied to detect the pathological changes of rat myocardium.Masson staining was used to observe the degree of myocardial tissue fibrosis.Western blot was used to detect the expressions of autophagy-and PI3K/AKT signaling pathway-related proteins in myocardial tissues.Results When compared to sham operation group,model group exhibited attenuated heart function,severe degrees of myocardial tissue damage and fibrosis,significantly reduced expressions of autophagy-and PI3K/AKT pathway-related proteins(P<0.05).When compared to model group,the degree of rat fibrosis were alleviated,and the expressions of autophagy-and PI3K/AKT pathway-related proteins were significantly increased in liraglutide group(P<0.05).When compared to liraglutide group,heart function was significantly reduced,and the degrees of myocardial tissue damage and fibrosis were severe,and autophagy-and PI3K/AKT pathway-related proteins was significantl

关 键 词：利拉鲁肽 急性心肌梗死 磷酸肌醇3激酶 蛋白激酶B 

分 类 号：R542.2[医药卫生—心血管疾病]