二甲双胍对心肌梗死后心脏功能的影响及其机制研究  

Protective Effect and Related Mechanism of Metformin on Cardiac Function After Myocardial Infarction

作　　者：周慧鑫 谌虎 刘志豪 周雨扬 李泽衍 许骁 陈华强 刘承哲 刘旨浩 王宇虹 王悦怡 赖燕秋 余锂镭[1] 江洪[1] ZHOU Huixin;CHEN Hu;LIU Zhihao;ZHOU Yuyang;LI Zeyan;XU Xiao;CHEN Huaqiang;LIU Chengzhe;LIU Zhihao;WANG Yuhong;WANG Yueyi;LAI Yanqiu;YU Lilei;JIANG Hong(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiac Autonomic Nervous System Research Center of Wuhan University,Cardiovascular Research Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院心血管内科,武汉大学心脏自主神经研究中心,武汉大学心血管病研究所,心血管病湖北省重点实验室,湖北武汉430060

出　　处：《心血管病学进展》2022年第3期265-268,共4页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(81871486,81530011);国家重点研发计划(2017YFC1307802)。

摘　　要：目的探讨二甲双胍对心肌梗死(MI)后心功能的影响及其作用机制。方法将28只健康Sprague Dawley大鼠随机分为3组:假手术组(n=8)、MI+生理盐水处理组(MI组,n=10)和MI+二甲双胍处理组(MET组,n=10)。采用结扎冠状动脉左前降支方法建立MI模型,假手术组冠状动脉左前降支穿线不结扎。按200 mg/kg给予二甲双胍或等量生理盐水,每日1次,连续干预4周。超声心动图测定心功能,分析心率变异性,检测心肌酪氨酸羟化酶(TH)密度。酶联免疫吸附测定法检测血清诱导型一氧化氮合酶(iNOS)水平,生化法检测心肌超氧化物歧化酶(SOD)和丙二醛(MDA)的水平。结果与假手术组比,MI组大鼠左室射血分数明显降低,心率变异性频域指标低频功率和低频/高频功率比值显著升高,TH密度显著增加,血清iNOS和心肌MDA水平显著升高,心肌SOD的水平显著降低(P<0.05);与MI组相比,MET组大鼠左室射血分数升高,低频功率和低频/高频功率比值降低,TH密度降低,血清iNOS和心肌MDA水平降低,心肌SOD水平升高(P<0.05)。结论二甲双胍可有效地改善慢性MI大鼠的心功能,可能通过抑制交感神经系统活性和降低氧化应激反应发挥作用。Objective To explore the effect and mechanism of metformin on cardiac function after myocardial infarction(MI).Methods Twenty-eight healthy Sprague Dawley rats were randomly divided into 3 groups:sham group(n=8),MI+saline group(MI group,n=10)and MI+metformin group(MET group,n=10).The MI model was established by ligating the left anterior descending coronary artery.In the sham group,the left anterior descending coronary artery was not ligated.Metformin or the same amount of normal saline were given at 200 mg/kg once a day for 4 weeks.Cardiac function was measured by echocardiography,heart rate variability was analyzed,and myocardial tyrosine hydroxylase(TH)density was detected.The levels of serum inducible nitric oxide synthase(iNOS)were detected by enzyme-linked immunosorbent assay,and the levels of myocardial superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by biochemical method.Results Compared with sham group,the left ventricular ejection fraction of rats in MI group decreased significantly,the frequency domain indexes of heart rate variability(low frequency power and low frequency/high frequency power ratio)increased significantly,the density of TH increased significantly,the levels of serum iNOS and myocardial MDA increased significantly,and the level of myocardial SOD decreased significantly(P<0.05).Compared with MI group,the left ventricular ejection fraction,low frequency power and low frequency/high frequency power ratio decreased,TH density decreased,serum iNOS and myocardial MDA levels decreased,and myocardial SOD levels increased in MET group(P<0.05).Conclusion Metformin can effectively improve the cardiac function of chronic MI rats,which may play a role by inhibiting the activity of sympathetic nervous system and reducing oxidative stress response.

关 键 词：二甲双胍 心肌梗死 交感神经系统 氧化应激 

分 类 号：R54[医药卫生—心血管疾病]