微创压力超负荷小鼠心衰模型的建立

A Mouse Model of Minimally Invasive Pressure Overload-induced Heart Failure Established through Suprasternal Notch Approach

目的通过胸骨上窝途径微创建立小鼠心衰模型。方法选用雄性昆明种系小鼠,经胸骨上窝利用钽夹部分夹闭主动脉弓,通过测量心脏体重比(HW/BW)、心脏超声以及组织学检查观察该方法创建小鼠心衰模型可行性。结果部分夹闭主动脉弓10周,HW/BW较假手术组明显增加(P<0.01);左室舒张期末直径(LVEDD)显著增大(P<0.01);左室后壁舒张期末厚度(LVPWD)明显变薄(P<0.01);射血分数(EF)以及短轴缩短率(FS)显著变小(P<0.01);夹闭部分主动脉弓10周后其血清氨基末端B型利钠肽前体(NT-pro BNP)较假手术组明显增加(P<0.01)。组织学观察左室部分心肌纤维排列紊乱、断裂,不同程度的结构破坏,心肌细胞呈不同程度变性及肥大,部分心肌细胞呈局灶性或片状坏死。结论经胸骨上窝途径部分夹闭主动脉弓建立小鼠心衰模型方法简单易行、微创、可靠。

Objective To establish a mouse model of pressure overload-induced heart failure via suprasternal notch approach. Methods Male mice were separated into a sham group and an experiment group. Through suprasternal notch approach, the aortic arch port between the origin of the right innominate and left common carotid arteries was partially clipped with tantalum clip, which had a remaining opening of 0.35 mm or 0.25 mm in diameter to cause progres- sively increased afterload. Echocardiography was performed 10 weeks after aortic arch clipped or sham surgery to deter- mine left ventricular end-diastolic diameter （LVEDD）, left ventricular end-systolic diameter （LVESD）, left ventricular posterior wall end-diastolic thickness （LVPWD）, ejection fraction （EF） and fractional shortening （FS）. After hemodynamic recordings were completed, mouse body weight （BW） and heart weight （HW） were measured for obtaining HW/BW ratio （mg/g）. After heart function examination, mice blood sample was collected for evaluation of serum N-terminal pro-brain natriuretic peptide （NT-proBNP）. At the end, part of left ventricular free wall was excised, and hematoxylin and eosin stain was made for histopathological examination. Results The HW/BW, LVEDD and serum NT-proBNP significantly increased in the experiment group compared with those in the sham group （P〈0.01, respectively）. The LVPWD, EF and FS significantly decreased compared with the sham group （P〈0.01, respectively）. Histopathological examination showed malalignment and rupture of cardiac muscle fibers, hypertrophy and degeneration of myocardial cells, part of which had local or patchy necrosis in left ventricule postoperatively 10 weeks. Conclusion The model of pressure overload-induced heart failure in mice established through suprasternal approach is simple, minimally invasive and reliable.