阿霉素诱导和腹主动脉缩窄术复制大鼠慢性心力衰竭模型的比较

Comparison of the two heart failure models in rats by abdominal aorta constriction and intraperitoneal injection of adriamycin

目的:通过阿霉素诱导和腹主动脉缩窄术分别建立大鼠慢性心力衰竭(CHF)模型,比较二者的优缺点,为后续实验选择合适的动物模型提供依据。方法:40只雄性SD大鼠随机分为三组,腹腔注射阿霉素诱导复制CHF模型组(ADR组,n=8)、腹主动脉缩窄术复制CHF模型组(AAC组,n=8)、假手术组(SO组,n=8,除不进行腹主动脉缩窄术外,其他制作程序与AAC组相同)。8周后在体检测大鼠心电图和心功能指标:心率(HR)、左室峰压(LVSP)、左室舒张期末压(LVEDP)、室内压变化速率(±dp/dtmax),计算大鼠心脏质量/体质量(HW/BW),并观察各组大鼠心肌形态学变化。结果:与SO组相比,ADR组与AAC组HW/BW均增加(P<0.01),(LVSP-LVEDP)×HR、LVSP、±dp/dtmax明显减低(P<0.01),LVEDP明显升高(P<0.01);病理切片显示SO组大鼠心肌纤维排列整齐、心肌细胞大小、形态正常,ADR组大鼠心肌细胞排列紊乱、胞质呈溶解状态、核深染,可见心肌纤维溶解断裂、心肌细胞间隙明显增宽,AAC组大鼠心肌纤维排列紊乱、心肌细胞肥大、间质中有炎症细胞浸润、间质增生。结论:腹腔注射阿霉素诱导及腹主动脉缩窄术均是复制大鼠CHF模型的有效方法,但前者操作简单、对大鼠损伤较小,大鼠病死率低,是我们后续实验较为理想的大鼠CHF模型选择。

Objective： To compare the advantages and disadvantages in developing chronic heart failure（ CHF） models in rats by either abdominal aorta constriction（ AAC） or intraperitoneal injection of adriamycin（ ADR） for evidence to select suitable animal models. Methods： Forty male SD rats were randomized into three groups to develop the animal models of CHF by either intraperitoneal injection of ADR（ ADR group,n = 8） or AAC（ AAC group,n = 8）. Sham operation group（ SO group,n = 8） were also included and developed as the procedure of AAC exclusive of abdominal aortic constriction. Electrocardiography（ ECG） was performed and cardiac function index were determined in all animals after 8 weeks,including heart rate（ HR）,left ventricular peak pressure（ LVSP）,left ventricular end-diastolic pressure（ LVEDP）,intra-ventricular pressure change rate（ ± dp/dtmax）. The heart weight/body weight（ HW/BW）were also measured in rats to observe the morphological changes of myocardium. Results： Compared with SO group,the HW/BW were significantly increased in both ADR and AAC groups（ P〈0. 01）,whereas（ LVSP-LVEDP） × HR,LVSP and ± dp /dtmax were significantly decreased,and LVEDP was distinctly elevated（ P〈0. 01）. Pathological section revealed that the myocardial fibers in rats of SO group were arranged in neat row with normal cell size and morphology. Contrarily,the myocardial cells in rats of group ADR were disorderly lined,with dissolved cytoplasm,hyperchromatic nuclei,dissolved fracture of myocardial fibers and widened intra-cellular space. In group AAC,rat myocardial fibers were disarrayed and the cardiomyocytes were hypertrophic,with interstitial inflammatory cell infiltration and hyperplasia. Conclusion： Although both AAC and intraperitoneal injection of ADR are effective techniques to develop rat models of CHF,yet the former appears a favorable option in experiment,for it has merits of simple performance,minor injury to the rats and lower death.