两种阿霉素心力衰竭模型及心功能进展的评估

Evaluation of two doxorubicin-induced heart failure models and changes of cardiac function

目的评估阿霉素心力衰竭动物模型的建模效果及其在不同实验阶段的心脏结构与功能改变。方法建立大鼠阿霉素心力衰竭动物模型,采用两种造模方法:(1)阿霉素模型1组为腹腔内注射阿霉素,每次2.5 mg/(kg·只),2周内注射6次,累积剂量15 mg/kg,造模周期为4周;(2)阿霉素模型2组6周内注射6次,造模周期为8周,其余相同。雄性Wistar大鼠24只,随机分为正常对照1组、阿霉素模型1组、正常对照2组、阿霉素模型2组,每组6只。超声心动图评估心脏结构和功能,苏木素-伊红(HE)染色评估心脏组织结构。结果超声心动图检测结果显示,阿霉素模型1组左室射血分数(LVEF)和左室短轴缩短率(LVFS)较正常对照1组差异有统计学意义(P=0.025,P=0.032)。HE染色2种阿霉素模型均存在细胞肥大、肌纤维纹理走向不规则,心肌细胞胞浆空泡化。评估心肌细胞间质纤维沉积面积,阿霉素模型1组高于正常对照1组(t=4.455,P=0.002),阿霉素模型2组与正常对照2组间差异有统计学意义(t=2.220,P=0.060)。阿霉素模型1组在实验中期、末期阶段心脏结构和功能呈动态改变。在整个实验周期中,心脏扩张明显,心脏左室收缩功能和舒张功能指标如二尖瓣血流速度、二尖瓣环心肌组织动度持续降低。右室功能指标如肺动脉峰流速及速度时间积分呈现先降低后升高的趋势。结论阿霉素模型1组建模成功。在整个实验周期,阿霉素模型1组心脏结构扩张,左室收缩功能和舒张功能持续降低。右室功能呈现实验中期降低、实验末期上调的动态变化。

Objective To evaluate the effects of two doxorubicin-induced heart failure models and changes of cardiac structure and function at different experiment stages.Methods Two doxorubicin-induced heart failure models were constructed.In the first model,rats received intraperitoneal injection of a cumulative dose of 15 mg/kg doxorubicin 6 times in 2 weeks[2.5 mg/(kg·rat)]and the cycle lasted for 4 weeks.In the second model,rats received intraperitoneal injection of a cumulative dose of 15 mg/kg doxorubicin 6 times in 6 weeks[2.5 mg/(kg·rat)]and the cycle lasted for 8 weeks.A total of 24 male Wistar rats were randomly divided into normal control group 1,doxorubicin model group 1,normal control group 2 and doxorubicin model group 2,with 6 rats in each group.Cardiac structure and function were detected using transthoracic echocardiography.Histopathology was evaluated using haematoxylin and eosin(HE)staining.Results Echocardiography showed left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in the doxorubicin model group 1 were significantly lower than those in normal control group 1(P=0.025,P=0.032).Stained with HE,tissue sections showed cardiomyocyte hypertrophy,irregular texture of muscle fibers,and intracellular vacuolation in both models.Doxorubicin model group 1 had significantly increased intercellular collagen deposition than normal control group 1(t=4.455,P=0.002),and doxorubicin model group 2 had significantly increased intercellular collagen deposition than normal control group 2(t=2.220,P=0.060).In doxorubicin model group 1,cardiac structure and function showed a dynamic development at the middle and end stages of the cycle.During the whole cycle,the heart obviously dilatated,left ventricular systolic and diastolic functional parameters including mitral flow and movement velocity of mitral valve kept decreasing,while the right ventricular functional parameters,such as pulmonary peak flow velocity and velocity time integral,reduced in the middle stage,but increased in the end stage.Conclusion The first doxorubicin model is successfully establishes.During the whole cycle,cardiac structure dilates,left ventricular systolic and diastolic function continuously worsened,while the right ventricular function decreases in the middle stage but mildly improves in the end stage.