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  

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[1] 张田田[1] 张俊峰[1] 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,S h anghai 201900,China)

机构地区：[1]上海交通大学医学院附属第九人民医院心内科,201900

出　　处：《国际心血管病杂志》2020年第5期293-297,共5页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81670316)。

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。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 C57 BL/6 mice aged 10-12 weeks were randomly divided into control group and surgery group.The left anterior descending branch of mice in the surgery group was ligated to establish the model of myocardial infarction,and according to the administration,the mice in the surgery group were further divided into the model group,the valsartan group and the LCZ696 group.Corn oil(the control group and the model group),valsartan(9.1 mg·kg^-1·d^-1)and LCZ696(20 mg·kg^-1·d^-1)were administered by oral gavage,respectively.Doppler echocardiogram detection and Masson staining of tissue sections were performed in all groups at multiple time points after myocardial infarction.Results:(1)Echocardiogram:after modeling the left ventricular ejection fraction(LVEF)of the mice in the model group gradually decreased,while that of the mice in the valsartan group and the LCZ696 group rose.Since the 7 th day after AMI,LVEF of the LCZ696 group was significantly higher than that of the model group(P<0.05);since the 14 th day after AMI,LVEF of the valsartan group was higher than that of the model group(P<0.05).At the 28 th and 42 nd day after AMI,LVEF of the LCZ696 group was higher than that of the valsartan group(P<0.05).(2)Masson staining:Masson staining was performed on the myocardial tissue of the same section in each group.Quantitative analysis of collagen fiber showed that each surgical group presented a certain degree of myocardial fibrosis over time,especially in the model group.And since the 7 th day after AMI,the proportion of fibrosis area in the valsartan group and the LCZ696 group were smaller than that of the model group(P<0.01).The proportion of fibrosis area in the LCZ696 group was smaller than that of the valsartan group since the 14 th day after AMI(P<0.05).Conclusions:LCZ696 is superior to valsartan alone in the early stage of acute myocardi

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 

分 类 号：R542.22[医药卫生—心血管疾病]