|本期目录/Table of Contents|

[1]刘东升 张侃迪 毕昌龙 张鹏 张田田 张俊峰.血管紧张素受体和脑啡肽酶双效抑制剂在急性心肌梗死早期的应用价值[J].国际心血管病杂志,2020,05:293-297.
　LIU Dongsheng,ZHANG Kandi,BI Changlong,et al.Application of angiotensin receptor-neprilysin inhibitor in early stage of acute myocardial infarction[J].International Journal of Cardiovascular Disease,2020,05:293-297.
点击复制

血管紧张素受体和脑啡肽酶双效抑制剂在急性心肌梗死早期的应用价值(PDF)

《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:
2020年05期
页码:
293-297
栏目:
基础研究
出版日期:
2020-10-15

文章信息/Info

Title:
Application of angiotensin receptor-neprilysin inhibitor in early stage of acute myocardial infarction
作者:
刘东升 张侃迪 毕昌龙 张鹏 张田田 张俊峰
201900 上海交通大学医学院附属第九人民医院心内科
Author(s):
LIU Dongsheng;  ZHANG Kandi;  BI Changlong;  ZHANG Peng;  ZHANG Tiantian;  ZHANG Junfeng
Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China
关键词:
血管紧张素受体和脑啡肽酶双效抑制剂;  急性心肌梗死;  心肌纤维化
Keywords:
Angiotensin receptor-neprilysin inhibitor;  Acute myocardial infarction;  Myocardial fibrosis
分类号:
-
DOI:
10.3969/j.issn.1673-6583.2020.05.010
文献标识码:
-
摘要:
目的:评估在小鼠急性心肌梗死(AMI)早期应用新型血管紧张素受体和脑啡肽酶双效抑制剂(ARNI)诺欣妥(LCZ696)的价值。方法:将10～12周龄健康雄性C57BL/6小鼠,随机分为对照组和手术组。手术组采用结扎左前降支法行心梗造模,按给药不同分为模型组、缬沙坦组和LCZ696组,分别予玉米油(对照组和模型组)、缬沙坦(9.1 mg?kg-1?d-1)和LCZ696(20 mg?kg-1?d-1)灌胃。于AMI后多个时间节点对所有小鼠心脏行超声多普勒检测和心肌组织Masson染色。结果:(1)心脏超声:对比造模后多时间节点结果发现,模型组小鼠左室射血分数(LVEF)逐渐下降,药物组均有所回升。自AMI后第7天开始,LCZ696组即明显高于模型组(P<0.05); 自AMI后第14天开始,缬沙坦组LVEF与模型组相比,差异有统计学意义(P<0.05); AMI后第28天和第42天,LCZ696组LVEF较缬沙坦组恢复更好(P均<0.05)。(2)Masson染色:对各组小鼠心脏同一切面的心肌组织行Masson染色,进行纤维化分析发现,各手术组随着时间进展,均表现出一定程度的心肌纤维化,以模型组更为明显,该组自AMI后第7天开始,即表现出较缬沙坦组和LCZ696组更大的纤维化面积占比(P<0.01); LCZ696组的心肌纤维化减轻程度自AMI后第14天开始便表现出与缬沙坦组的统计学差异(P<0.05)。结论:在小鼠AMI早期应用LCZ696优于单用缬沙坦,药效获益主要表现为改善LVEF和对抗心肌纤维化。
Abstract:
Objective:To evaluate the effects of angiotensin receptor-neprilysin inhibitor(ARNI)Entresto(LCZ696)in the early stage of acute myocardial infarction(AMI)in mice.Methods:Healthy male C57BL/6 mice aged 10-12 weeks were randomly divided into control group a

参考文献/References

[1] 胡盛寿, 杨跃进, 郑哲, 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] Zhang YH, Zhang J, Butler J, et al. Contemporary epidemiology, management, and outcomes of patients hospitalized for heart failure in China: results from the China Heart Failure(China-HF)Registry[J]. J Card Fail, 2017, 23(1):868-875.
[3] 张瑞岩, 高炜. 急性ST段抬高型心肌梗死诊断和治疗指南(2019)[J]. 中华心血管病杂志, 2019, 47(10):766-783.
[4] McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure[J]. N Engl J Med, 2014, 371(11):993-1004.
[5] Ibanez B, James S, Agewall S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation[J]. Kardiol Pol, 2018, 76(2):229-313.
[6] Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Failure Society of America[J]. Circulation, 2017, 136(6):e137-e161.
[7] Ishii M, Kaikita K, Sato K, et al. Cardioprotective effects of LCZ696(Sacubitril/Valsartan)after experimental acute myocardial infarction[J]. JACC Basic Transl Sci, 2017, 2(6):655-668.
[8] Hsiao HL, Langenickel TH, Greeley M, et al. Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol[J]. Clin Pharmacol Drug Dev, 2015, 4(6):407-417.
[9] 刘岳, 汪芳. 沙库巴曲缬沙坦的药代动力学和药效学特点[J]. 中国循环杂志, 2018, 33(2):198-200.
[10] Akahori M, Ayalasomayajula S, Langenickel T, et al. Pharmacokinetics after single ascending dose, food effect, and safety of Sacubitril/Valsartan(LCZ696), an angiotensin receptor and neprilysin inhibitor, in healthy Japanese subjects[J]. Eur J Drug Metab Pharmacokinet, 2017, 42(3):407-416.
[11] Leong DP, McMurray JJV, Joseph PG, et al. From ACE inhibitors/ARBs to ARNIs in coronary artery disease and heart failure(Part 2/5)[J]. J Am Coll Cardiol, 2019, 74(5):683-698.
[12] Mangiafico S, Costello-Boerrigter LC, Andersen IA, et al. Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics[J]. Eur Heart J, 2013, 34(12):886-893.
[13] Li P, Wang D, Lucas J, et al. Atrial natriuretic peptide inhibits transforming growth factor beta-induced Smad signaling and myofibroblast transformation in mouse cardiac fibroblasts[J]. Circ Res, 2008, 102(2):185-192.
[14] Kapoun AM, Liang F, O'Young G, et al. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation[J]. Circ Res, 2004, 94(4):453-461.
[15] Izumiya Y, Araki S, Usuku H, et al. Chronic C-type natriuretic peptide infusion attenuates angiotensin Ⅱ-induced myocardial superoxide production and cardiac remodeling[J]. Int J Vasc Med, 2012, 2012:246058.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金(81670316)
通信作者:张俊峰,E-mail:jfzhang_dr@163.com
更新日期/Last Update: 2020-10-15