利拉鲁肽对糖尿病合并心肌梗死小鼠心功能的影响及其作用机制  

Effect of liraglutide on cardiac function of mice with diabetes mellitus and concomitant myocardial infarction and its mechanism

作　　者：刘晓玲[1] 陈桂艳 伍明文 王婉 高宁 李雪晶 杨云芳 梁旭 阳柳雪 LIU Xiaoling;CHEN Guiyan;WU Mingwen;WANG Wan;GAO Ning;LI Xuejing;YANG Yunfang;LIANG Xu;YANG Liuxue(Department of Endocrinology,Affiliated Hospital of Guilin Medical University,Guilin 541001,Guangxi,China;Department of Endocrinology,the Second Affiliated Hospital of Guilin Medical University,Guilin 541199,Guangxi,China;Teaching and Research Section for Health Toxicology of Public Health School,Guilin Medical University,Guilin 541001,Guangxi,China;Department of Cardiovascular Medicine,the Second Affiliated Hospital of Guilin Medical University,Guilin 541199,Guangxi,China)

机构地区：[1]广西桂林医学院附属医院内分泌科,广西桂林市541001 [2]桂林医学院第二附属医院内分泌科,广西桂林市541199 [3]桂林医学院公共卫生学院卫生毒理教研室,广西桂林市541001 [4]桂林医学院第二附属医院心血管内科,广西桂林市541199

出　　处：《广西医学》2024年第2期270-275,共6页Guangxi Medical Journal

基　　金：广西自然科学基金(2020GXNSFAA238036)。

摘　　要：目的探讨利拉鲁肽对糖尿病合并心肌梗死小鼠心功能的影响及其作用机制。方法按随机数字表法将75只KM雄性小鼠分为对照组15只和模型处理组60只。对模型处理组的60只小鼠建立糖尿病小鼠模型,建模成功后再按随机数字表法选取模型处理组的45只小鼠建立糖尿病合并心肌梗死小鼠模型,剩余的15只小鼠作为假手术组,且仅对小鼠开胸而不结扎冠状动脉。将45只糖尿病合并心肌梗死小鼠模型按随机数字表法分为模型组(n=15)、心梗干预组(n=15)、糖干预组(n=15),给予心梗干预组小鼠灌胃硫酸氢氯吡格雷+阿托伐他汀钙片干预,给予糖干预组小鼠腹腔注射利拉鲁肽注射液干预,其余小鼠均不做特殊处理。干预7d后,使用心电图机观察各组小鼠的心电图,采用HE染色及2,3,5-氯化三苯四氮唑染色观察各组小鼠的病理情况及心肌梗死面积,采用Western blot检测各组小鼠心肌组织磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、糖原合成酶激酶3β(GSK-3β)的蛋白表达量。结果(1)对照组、假手术组小鼠心电图无明显异常,模型组小鼠心电图存在明显的ST段抬高及变异T波,心梗干预组、糖干预组小鼠心电图ST段抬高及变异T波较模型组明显改善,且心梗干预组的改善效果优于糖干预组。(2)对照组、假手术组小鼠心肌纤维排列整齐紧凑,心肌细胞形态完整;相比于对照组、假手术组,模型组小鼠心肌组织可见梗死区,梗死周边区域心肌细胞形态不完整,排列混乱,有大量炎症细胞浸润和纤维组织增生;相比于模型组,心梗干预组和糖干预组小鼠上述病理改变程度均得到改善,心梗干预组改善程度优于糖干预组。(3)与对照组相比,假手术组小鼠心肌梗死区面积百分比无明显变化(P>0.05);与对照组和假手术组相比,模型组小鼠的心肌梗死区面积百分比明显增加(P<0.05);与模型组相比,心梗干预组与糖干预组小鼠的Objective To explore the effect of liraglutide on cardiac function of mice with diabetes mellitus and concomitant myocardial infarction and its mechanism.Methods A total of 75 KM male mice were assigned to control group(15 mice)or model treatment group(60 mice)according to the random number table method.The diabetic mice model was established on 60 mice in the model treatment group,after successful modeling,the mice model of diabetes mellitus and concomitant myocardial infarction was established in 45 mice of the model treatment group selected by the random number table method;moreover,the remaining 15 mice were taken as sham operation group,and mice only underwent thoracotomy without coronary artery ligation.A total of 45 mice with diabetes mellitus and concomitant myocardial infarction were assigned to model group(n=15),myocardial infarction intervention group(n=15),or glucose intervention group(n=15)according to the random number table method,therein the myocardial infarction intervention group received intragastric administration of clopidogrel bisulfate+atorvastatin calcium tablets for intervention,the glucose intervention group was intervened by intraperitoneal injection of liraglutide injection,and the remaining mice did not receive any special treatment.After 7 days of intervention,electrocardiogram of mice in various groups was observed by using the electrocardiogram machine.The HE staining and 2,3,5-triphenyltetrazolium chloride staining were used to observe pathological status and myocardial infarction size of mice in various groups.The Western blot was used to detect protein expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),and glycogen synthetase kinase 3β(GSK-3β)in myocardial tissues of mice in various groups.Results(1)There was no obvious abnormality in electrocardiogram of the control group and the sham operation group,and there was obvious ST-segment elevation and variant T wave in electrocardiogram of mice in the model group.ST-segment elevation and variant T wave of ele

关 键 词：糖尿病 心肌梗死 利拉鲁肽 磷脂酰肌醇3激酶 蛋白激酶B 糖原合成酶激酶3Β 作用机制 小鼠 

分 类 号：R587.1[医药卫生—内分泌]