CAJ | 학술논문

目的尝试一种新的用以观察左心室压力超负荷诱导左心室肥厚的主动脉弓缩窄动物模型.方法 55只小鼠随机数字法分为重度缩窄组(sTAC,27只),中度缩窄组(mTAC,7只)以及假手术组(sham,21只).采用微创改进的方法,在无名动脉和左颈总动脉之间结扎主动脉弓,构建不同程度的主动脉缩窄,造成中度或重度的左心室流出道机械梗阻.使用经胸二维以及M型超声监测术后4周压力超负荷诱导左心室肥厚的可靠性并评价其效果.结果成功建立34只小鼠模型,存活率88.2％(30/34只),手术小鼠术后顺利存活4周以上.主动脉弓缩窄后4周,经胸超声证实小鼠心脏呈现离心性肥厚表现,心脏收缩功能降低,主动脉弓中度缩窄小鼠的左心室短轴缩短分数(LVFS)从0.403±0.007降至0.340±0.015 (P ＜0.05),左心室较好地保留了收缩和舒张功能,心室肥厚呈代偿性;重度缩窄小鼠LVFS从0.438±0.011降至0.216±0.012(P＜0.01),心脏收缩功能明显减退,室壁活动僵硬甚至局部无活动,呈病理性失代偿性肥厚.结论微创方法在无名动脉和左颈总动脉之间结扎主动脉弓,构建不同程度的主动脉缩窄模型可重复性好,效果确切,术后小鼠存活率高,是一种值得推荐的左心室压力超负荷模型.
목적 상시일충신적용이관찰좌심실압력초부하유도좌심실비후적주동맥궁축착동물모형.방법 55지소서수궤수자법분위중도축착조(sTAC,27지),중도축착조(mTAC,7지)이급가수술조(sham,21지).채용미창개진적방법,재무명동맥화좌경총동맥지간결찰주동맥궁,구건불동정도적주동맥축착,조성중도혹중도적좌심실류출도궤계경조.사용경흉이유이급M형초성감측술후4주압력초부하유도좌심실비후적가고성병평개기효과.결과 성공건립34지소서모형,존활솔88.2％(30/34지),수술소서술후순리존활4주이상.주동맥궁축착후4주,경흉초성증실소서심장정현리심성비후표현,심장수축공능강저,주동맥궁중도축착소서적좌심실단축축단분수(LVFS)종0.403±0.007강지0.340±0.015 (P ＜0.05),좌심실교호지보류료수축화서장공능,심실비후정대상성;중도축착소서LVFS종0.438±0.011강지0.216±0.012(P＜0.01),심장수축공능명현감퇴,실벽활동강경심지국부무활동,정병이성실대상성비후.결론 미창방법재무명동맥화좌경총동맥지간결찰주동맥궁,구건불동정도적주동맥축착모형가중복성호,효과학절,술후소서존활솔고,시일충치득추천적좌심실압력초부하모형.
Objective To explore the feasibility of establishing a modified mouse model of pressure overload induced left ventricular hypertrophy by transverse aortic constriction(TAC).Methods 55 C57BL/6 female mice were randomly divided into three groups:severe TAC group (n =27),moderate TAC group (n =7) and sham surgery group (n =21),respectively.By ligating the aorta arch between innominate artery and the left common carotid artery with modified techniques in a minimally invasive way,moderate or severe aortic constriction were established successfully and reliably to mimic left ventricular(LV)outflow obstruction; to correctly evaluate the cardiac structural and functional responses to aortic arch banding,2-dimention (2D) and M mode transthoracic echocardiography (TTE) were deployed to monitor the LV contractile function and assess the LV hypertrophic changes induced by pressure overload at 4 weeks after the surgery.Results The mouse model of aortic constriction was established successfully with a post-operative survival rate more than 88％.And all these operated mice were able to survive at least 4 weeks long.Eccentric left ventricular hypertrophic changes were detected with echocardiographic measurement 4 weeks after the banding operation in both mTAC and sTAC group,as dilated left ventricular lumen with enlarged LV end-diastolic dimension (LVEDD) and LV end systolic-dimension (LVESD) were confirmed.Mice with moderate banded aorta exhibited a compensated LV hypertrophy with preserved contractile functions and satisfactory ventricular wall movements to some extent,although left ventricular fractional shorting (LVFS) reduced gradually from 0.403 ± 0.007 to 0.340 ± 0.015 (P＜0.05) ; while in severe banded (sTAC) mice,LVFS reduced more significantly as a sharp decrease from 0.438 ± 0.011 to 0.216 ± 0.012 (P ＜ 0.01) were detected,combined with poor contractile function and stiff ventricular wall movements,exhibiting a de-compensated pathological left ventricular hypertrophy.Conclusion This modified TAC opcration could be easily carried out,and the TAC mouse model mentioned in the present research was an effective pressure overload model with several superiorities including less trauma,improved post-operative survival rate,rapid recovery and satisfactory reproducibility,thus a better and recommended mouse model for specific research purpose concerning LV hypertrophy mechanistic studies.