三种心脏重塑小鼠模型构建方法及其效果评价  

Establishment and Assessment of Three Mice Model of Cardiac Remodeling

作　　者：周心涛[1] 张碧雪 董禹辰 酉鹏华 程征 ZHOU Xintao;ZHANG Bixue;DONG Yuchen;YOU Penghua;CHENG Zheng(Department of Cardiology,Sinopharm Dongfeng General Hospital Affiliated to Hubei University of Medicine/Hubei Clinical Research Center of Hypertension,Shiyan 442001,China;Department of Otorhinolaryngology,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830092,China;Burn and Plastic Surgery,the Second Affiliated Hospital of Air Force Medical University,Xi'an 710032,China;Department of Cardiology,Shaanxi Provincial People's Hospital,Xi'an 710068,China;Department of Cardiovascular Internal Medicine,the Second Affiliated Hospital of Harbin Medical Sciences University,Harbin 150086,China;Department of Cardiology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]湖北医药学院附属国药东风总医院心内科,湖北省高血压临床医学研究中心,湖北省十堰市442001 [2]新疆医科大学第六附属医院耳鼻喉科,新疆维吾尔自治区乌鲁木齐市830092 [3]空军军医大学第二附属医院烧伤整形外科,陕西省西安市710032 [4]陕西省人民医院心血管内科,陕西省西安市710068 [5]哈尔滨医科大学第二附属医院心血管内科,黑龙江省哈尔滨市150086 [6]西安交通大学第二附属医院心血管内科,陕西省西安市710004

出　　处：《实用心脑肺血管病杂志》2025年第3期72-79,共8页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：国家自然科学基金面上项目(82070282);中国博士后基金面上项目(2022MD723777);黑龙江省博士后基金面上项目(LBH-Z22216);陕西省重点研发项目(2023-YBSF-346)。

摘　　要：目的分别采用血管紧张素Ⅱ(AngⅡ)微泵泵入法、主动脉弓缩窄(TAC)法、阿霉素诱导法构建心脏重塑小鼠模型并评估其效果。方法选取12周龄一级清洁雄性C57BL/6小鼠36只,采用电脑生成随机数字的方法将36只小鼠分为对照组(不做任何处理)、A组(采用AngⅡ微泵泵入法构建心脏重塑小鼠模型)、B组(采用TAC法构建心脏重塑小鼠模型)、C组(采用阿霉素诱导法构建心脏重塑小鼠模型),每组9只。建模周期均为3周。建模结束后,观察各组小鼠基本情况,采用M型超声检测小鼠心脏功能及结构指标[左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)],采用侵入性血流动力学检测方法检测血流动力学指标[心率、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、室内压最大上升速率(+dp/dtmax)、室内压最大下降速率(-dp/dtmax)],测量心脏重量/体质量比,采用苏木精-伊红(HE)、天狼星红、麦胚凝集素染色检测心肌组织病理学情况,采用RT-PCR检测α-平滑肌肌动蛋白(α-SMA)、心房利钠因子(ANF)mRNA相对表达量,采用免疫印迹法检测α-SMA、ANF蛋白表达水平。结果对照组、A组、B组小鼠存活率为100.0%,C组小鼠存活率为88.9%。建模结束后,与对照组相比,A组小鼠活动度和进食情况均无明显变化;B组小鼠活动度明显减少,并伴有呼吸频率增快、精神萎靡、进食减少、饮水增多;C组小鼠活动度略有减少,毛发晦暗且脱落。B、C组小鼠LVEF和LVFS低于对照组,LVESD大于对照组(P<0.05)。A、B、C组小鼠心率快于对照组,LVSP高于对照组(P<0.05);B、C组小鼠LVEDP高于对照组,-dp/dtmax低于对照组(P<0.05)。B组小鼠心脏重量/体质量比高于对照组(P<0.05)。A组小鼠心肌组织出现部分横纹破坏、心肌纤维排列紊乱且伴有炎性细胞浸润;B组小鼠心肌受损较严重,部分心肌细胞可见空泡样变性、�Objective To construct the mice model of cardiac remodeling by angiotensinⅡ(AngⅡ)micropump pumping method,aortic arch constriction(TAC)method and adriamycin induction method,and evaluate their effect.Methods Thirty-six 12-week-old clean male C57BL/6 mice were randomly divided into control group(without any treatment),group A(AngⅡmicropump pumping method was used to construct the mouse model of cardiac remodeling),group B(TAC method was used to construct mouse model of cardiac remodeling),group C(adriamycin induction method was used to construct mouse model of cardiac remodeling),with 9 mice in each group.The modeling period was 3 weeks.After modeling,the basic situation of mice in each group was observed,the cardiac function and structural indexes of mice[left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD)]were detected by M-mode ultrasound,hemodynamic parameters[heart rate,left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),positive rate of increase in left ventricular pressure during isovolumic systole(+dp/dtmax),negative rate of increase in left ventricular pressure during isovolumic systole(-dp/dtmax)]were detected by invasive hemodynamic detection method,the ratio of heart weight to body weight was measured,myocardial histopathology was detected by hematoxylin-eosin(HE),Sirius red and wheat germ agglutinin staining,the relative expression ofα-smooth muscle actin(α-SMA)and atrial natriuretic factor(ANF)mRNA was detected by RT-PCR,and the protein expression levels ofα-SMA and ANF were detected by Western blotting.Results The survival rate of mice in the control group,group A and group B was 100.0%,and the survival rate of mice in group C was 88.9%.After the modeling,compared with the control group,there was no significant change in the activity and eating of mice in group A;the activity of mice in group B was significantly reduced,accompanie

关 键 词：心脏重塑 血管紧张素Ⅱ 主动脉缩窄 阿霉素 小鼠 

分 类 号：R331.31[医药卫生—人体生理学]