小鼠非开胸式主动脉弓狭窄心衰模型的构建及评价  

Construction and evaluation of a model of heart failure in mice with non-thoracic aortic arch stenosis

作　　者：方明笋[1,3] 金栌帅 张利棕 马全鑫[1] 金璐[2] 郎佳丽 傅惠英 寿旗扬 FANG Minsun;JIN Lushuai;ZHANG Lizong;MA Quanxin;JIN Lu;LANG Jiali;FU Huiying;SHOU Qiyang(Animal Experimental Research Center/Institute of Comparative Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China;Second Clinical Medical College/Affiliated SecondaryHospital,Zhejiang ChineseMedical University,Hangzhou 310053;College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027)

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究所,杭州310053 [2]浙江中医药大学第二临床医学院/附属第二医院,杭州310053 [3]浙江大学化学工程与生物工程学院,杭州310027

出　　处：《中国比较医学杂志》2020年第3期14-19,共6页Chinese Journal of Comparative Medicine

基　　金：浙江中医药大学科研基金资助(2017ZY19);国家自然科学基金(81673645,81873047,81573677)。

摘　　要：目的采用非开胸式主动脉弓狭窄术(transverse aortic constriction,TAC)建立稳定可靠的小鼠心力衰竭模型,并对小鼠心力衰竭的的病理进程进行分析观察。方法采用非开胸式TAC术建立C57BL/6J小鼠心力衰竭模型,通过心动超声成像,左心室质量指数,病理组织学检查来评价心脏功能及心衰程度。结果左心室质量指数随时间逐渐升高,与假手术组比,术后4周、8周、12周均有非常显著性差异(P<0. 01)。心动超声显示,与假手术组相比,TAC术后4周左心室前壁厚度、左心室校正重量(LV mass corrected),心率(heart rate,HR),心输出量(cardiac output,CO)显著增加(P<0. 01)。术后8周左心室壁厚度、左心室校正重量和左心室收缩末期容积(LV Vol;s)显著增加(P<0. 01),射血分数(ejection fraction,EF)和短轴率(fractional shortening,FS)显著减小(P<0. 01)。TAC术后12周,左室舒张末期内径(LVID;d)、左室收缩末期内径(LVID;s)、左心室舒张末期容积(LV Vol;d)和左心室收缩末期容积(LV Vol;s)显著增加(P<0. 01),射血分数和短轴率进一步降低(P<0. 01),同时病理学检查显示心肌纤维不同程度异常或病变。结论实验结果表明,采用非开胸式TAC术建立小鼠心衰模型稳定可行,能够模拟的人类压力超负荷导致的左心室肥厚到心力衰竭的病理生理过程。Objective Transverse aortic constriction( TAC) was used to establish a stable and reliable model of heart failure in mice,and the pathological process of heart failure in mice was analyzed and observed. Methods The heart failure model of C57 BL/6 J mice was established by non-thoracotomy TAC. The heart function and degree of heart failure were evaluated by echocardiography,left ventricular mass index,and histopathological examination. Results The left ventricular mass index gradually increased overtime. Compared with that in the sham-operated group,there were significant differences in left ventricular mass index at 4,8,and 12 weeks after operation( P< 0. 01). Echocardiography showed that the left ventricular anterior wall thickness,left ventricular corrected weight,heart rate,and cardiac output increased significantly 4 weeks after TAC compared with those in the sham operation group( P < 0. 01). Left ventricular wall thickness,left ventricular corrected weight,and left ventricular end systolic volume increased significantly( P < 0. 01),while ejection fraction and fractional shortening decreased significantly( P<0. 01). At 12 weeks after TAC,left ventricular enddiastolic diameter, left ventricular endsystolic diameter, left ventricular enddiastolicvolume, and left ventricular endsystolic volumeincreased significantly( P < 0. 01),ejection fraction and fractional shortening decreased further( P <0. 01),and pathological examination showed that myocardial fibers were abnormal tovarying degrees and lesional.Conclusions The experimental result show that the establishment of a mouse heart failure model by non-thoracotomy TAC is stable and feasible,and can simulate the pathophysiological process from left ventricular hypertrophy to heart failure caused by human pressure overload.

关 键 词：心衰模型 主动脉弓狭窄术 小鼠 

分 类 号：R-33[医药卫生]