[1]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 江洪.二甲双胍对心肌梗死后心脏功能的影响及其机制研究[J].心血管病学进展,2022,(3):265-268.[doi:10.16806/j.cnki.issn.1004-3934.2022.03.000]
点击复制

二甲双胍对心肌梗死后心脏功能的影响及其机制研究()
分享到：

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2022年3期
页码:
265-268
栏目:
论著
出版日期:
2022-03-25

文章信息/Info

Title:
Protective Effect and Related Mechanism of Metformin on Cardiac Function After Myocardial Infarction
文章编号:
202106010
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 江洪
(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)
Author(s):
?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,Huhei,China)
关键词:
二甲双胍; 心肌梗死; 交感神经系统; 氧化应激
Keywords:
Metformin; Myocardial infarction; Sympathetic nervous system; Oxidative stress
DOI:
10.16806/j.cnki.issn.1004-3934.2022.03.000
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。
Abstract:
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

参考文献/References:

[1] 胡盛寿,高润霖,刘力生,等. 《中国心血管病报告2018》概要[J]. 中国循环杂志,2019,34(3):209-220.

[2] Lymperopoulos A,Rengo G,Koch WJ. Adrenergic nervous system in heart failure:pathophysiology and therapy[J]. Circ Res,2013,113(6):739-753.

[3] Han S,Kobayashi K,Joung B,et al. Electroanatomic remodeling of the left stellate ganglion after myocardial infarction[J]. J Am Coll Cardiol,2012,59(10):954-961.

[4] Foretz M,Guigas B,Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus[J]. Nat Rev Endocrinol,2019,15(10):569-589.

[5] Foretz M,Guigas B,Bertrand L,et al. Metformin:from mechanisms of action to therapies[J]. Cell Metab,2014,20(6):953-966.

[6] Peuler JD. Opposing adrenergic actions of intravenous metformin on arterial pressure in female spontaneously hypertensive rats[J]. Cardiovasc Res,1999,43(1):237-247.

[7] Dean A,Nilsen M,Loughlin L,et al. Metformin reverses development of pulmonary hypertension via aromatase inhibition[J]. Hypertension,2016,68(2):446-454.

[8] Lu L,Ye S,Scalzo RL,et al. Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs[J]. Diabetologia,2017,60(8):1550-1558.

[9] Oliveira PWC,de Sousa GJ,Birocale AM,et al. Chronic metformin reduces systemic and local inflammatory proteins and improves hypertension-related cardiac autonomic dysfunction[J]. Nutr Metab Cardiovasc Dis,2020,30(2):274-281.

[10] Wang Y,Jiang W,Chen H,et al. Sympathetic nervous system mediates cardiac remodeling after myocardial infarction in a circadian disruption model[J]. Front Cardiovasc Med,2021,8:668387.

[11] Kalyani RR. Glucose-lowering drugs to reduce cardiovascular risk in type 2 diabetes[J]. N Engl J Med,2021,384(13):1248-1260.

[12] Bromage DI,Godec TR,Pujades-Rodriguez M,et al. Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes:a cohort study[J]. Cardiovasc Diabetol,2019,18(1):168.

[13] Li J,Minczuk K,Massey JC,et al. Metformin improves cardiac metabolism and function,and prevents left ventricular hypertrophy in spontaneously hypertensive rats[J]. J Am Heart Assoc,2020,9(7):e015154.

[14] Bairey Merz CN,Elboudwarej O,Mehta P. The autonomic nervous system and cardiovascular health and disease:a complex balancing act[J]. JACC Heart Fail,2015,3(5):383-385.

[15] Kupper N,Denollet J,Widdershoven J,et al. Cardiovascular reactivity to mental stress and mortality in patients with heart failure[J]. JACC Heart Fail,2015,3(5):373-382.

[16] Yu L,Zhou L,Cao G,et al. Optogenetic modulation of cardiac sympathetic nerve activity to prevent ventricular arrhythmias[J]. J Am Coll Cardiol,2017,70(22):2778-2790.

[17] Scheer FAJL,Chellappa SL,Hu K,et al. Impact of mental stress,the circadian system and their interaction on human cardiovascular function[J]. Psychoneuroendocrinology,2019,103:125-129.

[18] Lehmann LH,Rostosky JS,Buss SJ,et al. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling[J]. Proc Natl Acad Sci U S A,2014,111(37):13499-13504.

[19] Bae J,Salamon RJ,Brandt EB,et al. Malonate promotes adult cardiomyocyte proliferation and heart regeneration[J]. Circulation,2021,143(20):1973-1986.

[20] Henderson BC,Tyagi N,Ovechkin A,et al. Oxidative remodeling in pressure overload induced chronic heart failure[J]. Eur J Heart Fail,2007,9(5):450-457.

[21] Feng L,Yang X,Liang S,et al. Silica nanoparticles trigger the vascular endothelial dysfunction and prethrombotic state via miR-451 directly regulating the IL6R signaling pathway[J]. Part Fibre Toxicol,2019,16(1):16.

[22] Kimura Y,Hirooka Y,Sagara Y,et al. Overexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase in oxidative stress[J]. Circ Res,2005,96(2):252-260.

相似文献/References:

[1]王铁华,郑景辉,莫云秋.蛋白质组学在心肌梗死中的研究进展[J].心血管病学进展,2015,(5):616.[doi:10.3969/j.issn.1004-3934.2015.05.024]
　WANG Tiehua,ZHENG Jinghui,MO Yunqiu.Research Progress of Proteomics in Myocardial Infarction[J].Advances in Cardiovascular Diseases,2015,(3):616.[doi:10.3969/j.issn.1004-3934.2015.05.024]
[2]孙洋.基质金属蛋白酶与心肌梗死后心脏重构[J].心血管病学进展,2019,(8):1094.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.006]
　SUN Yang.Matrix Metalloproteinases in Cardiac Remodeling after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2019,(3):1094.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.006]
[3]陈丰 苏强 朱继金.高迁移率族蛋白B1在心脏炎症反应性疾病中的研究进展[J].心血管病学进展,2019,(8):1111.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.010]
　CHEN Feng,SU Qiang,ZHU Jijin.Research Progress of HMGB1 in Myocardial Inflammatory Reactivity Disease[J].Advances in Cardiovascular Diseases,2019,(3):1111.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.010]
[4]常文婧 王丽娜.Hippo通路在心脏发育、再生和疾病中的作用[J].心血管病学进展,2019,(8):1115.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.011]
　CHANG Wenjin,WANG Lina.Role of Hippo Pathway in Heart Development,Regeneration and Disease[J].Advances in Cardiovascular Diseases,2019,(3):1115.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.011]
[5]王宇 周思维 张莎 吴弘.植入型心律转复除颤器在心肌梗死后心脏性猝死中的研究进展[J].心血管病学进展,2020,(1):4.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.002]
　WANG Yu,ZHOU Siwei,ZHANG Sha,et al.Implantable Cardioverter Defibrillator in Sudden Cardiac Death after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2020,(3):4.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.002]
[6]邹先明 赵然尊.长链非编码RNA ANRIL与心血管疾病的研究进展[J].心血管病学进展,2020,(2):167.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.017]
　ZOU Xianming,ZHAO Ranzun.Long Non-Coding RNA ANRIL and Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2020,(3):167.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.017]
[7]王茜 李晶洁.细胞学机制在调控心肌梗死后炎症反应中的研究进展[J].心血管病学进展,2020,(2):190.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.023]
　WANG QianLI Jingjie.Cytological Mechanisms in Regulation of The Post-infarction Inflammatory Response[J].Advances in Cardiovascular Diseases,2020,(3):190.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.023]
[8]黄柳,张瑞宁,田小超,等.内皮祖细胞与冠心病患者CD14CD16+单核细胞共培养后移植心肌梗死大鼠对血管密度及心肌梗死面积的影响[J].心血管病学进展,2020,(2):203.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.027]
　HUANG Liu,ZHANG Ruining,TIAN Xiaochao,et al.Effects of Co-cultured Endothelial Progenitor Cells and CD14++CD16+ Monocytes from Coronary Heart Disease Patients on Vascular Density and Myocardial Infarction Size in Transplanting Myocardial Infarction Rats[J].Advances in Cardiovascular Diseases,2020,(3):203.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.027]
[9]刘玉婷,贾锋鹏.骨膜蛋白与心血管疾病的研究进展[J].心血管病学进展,2020,(3):239.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.006]
　LIU Yuting,JIA Fengpeng.Roles of Periostin in Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2020,(3):239.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.006]
[10]谢建华,赵鸿泽,刘剑雄.MicroRNA在心肌梗死后左室重塑和心力衰竭发展中的研究现状[J].心血管病学进展,2020,(3):259.[doi:10.16806 /j.cnki.issn.1004-3934.2020.03.011]
　XIE Jianhua,ZHAO Hongze,LIU Jianxiong.MicroRNA in Development of Left Ventricular Remodeling and Heart Failure after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2020,(3):259.[doi:10.16806 /j.cnki.issn.1004-3934.2020.03.011]

更新日期/Last Update: 2022-04-20