心力衰竭小型动物模型研究进展

Small Animal Models of Heart Failure

心力衰竭是一种临床常见的心血管综合征,其发病率与死亡率不断上升,威胁着人类健康。心力衰竭的致病因素复杂,血流动力学异常,心室负荷增加导致心肌肥厚,神经内分泌细胞因子过度激活引发心室重构等原因均会导致心衰症状。然而,对心衰的发病机制和干预治疗的研究远没达到临床要求,进一步了解心衰的机制和寻找更有效的药物和手段是目前亟需的。心衰动物模型通过多种手段模拟人类心衰的发病过程,能提供心衰的发病机制及防治的科学基础和理论依据。由于大型动物心衰模型对基础实验设备及操作技术要求较高,加之造模成本昂贵,故而在进行药效筛选及机制研究中,常选用成本低廉且操作相对简便的小型心衰动物模型。常用的小型动物心衰模型按造模原理可分为压力负荷型、心脏缺血型、心脏抑制型等,造模方法主要包括主动脉缩窄法、肺动脉高压法、盐负荷法、冠状动脉结扎法、阿霉素法、异丙肾上腺素法、戊巴比妥钠法、普罗帕酮法等。各种造模方法复制的心衰模型具有其各自的发病原理和特点,因此在选择心衰动物模型进行实验研究时应综合考虑实验目的、基础设备、实验经费等。

Heart failure（ HF） is a common clinical cardiovascular syndrome. The rising morbidity and mortality of HF has threatened human health. The causes for HF are complicated. Hemodynamic abnormalities and ventricular overload lead to myocardial hypertrophy,and excessive activation of neuroendocrine cell factor causes ventricular remodeling,all of which can lead to HF symptoms. Because the existing studies on the pathogenesis and treatment in HF don＇t meet clinical requirements,it urgently needs to further study the pathogenic mechanism and find more effective drugs or therapeutic approaches. HF animal models can simulate disease in human by various means,and provide scientific and theoretical basis for pathogenesis,treatment and prevention of HF. Due to higher requirements of large animal model of HF for experiment equipment and technical operation,as well as a high cost,small animal models of heart failure with a low cost and simple operation have often been used in screening drug efficacy and studying mechanisms. According to the principle,commonly used small animal models of HF can be divided into pressure overload type,heart ischemia type and cardiac inhibition type,and the modeling methods mainly include aorta coarctation, pulmonary hypertension, salt load, coronary artery occlusion, adriamycin,isopropyl adrenaline,pentobarbital sodium and propafenone. Animal models of HF made by various methods have various principle and characteristics. Therefore, purpose of experiment, infrastructure and funds shall be considered in choosing animal model for study.