心肌病动物模型:从分子机制解析到临床转化的核心桥梁OA

Cardiomyopathies,a heterogeneous group of myocardial disorders,represent a principal cause of heart failure and sudden cardiac death,necessitating precise animal models to dissect their complex pathophysiology.This re-view systematically evaluates the key animal models used in research on dilated cardiomyopathy(DCM),hypertrophic car-diomyopathy(HCM),arrhythmogenic cardiomyopathy(ACM),and restrictive cardiomyopathy(RCM),and points out that their scientific value depends on specific research objectives.Small animal models,exemplified by mice and ze-brafish,serve as the cornerstone for elucidating initial molecular pathogenesis,owing to their short breeding cycles,low husbandry costs,high-throughput screening potertial and mature genetic eding systems.In contrast,large animal models,such as swine and canines,constitute a critical platform for preclinical evaluation of pharmacological and device-based ther-apies,given their high fidelity to human cardiac physiology,hemodynamics,and disease progression.The analytical framework of this review is tightly coupled to disease etiology:for HCM,ACM and RCM,which are predominantly driven by monogenic mutations,this review focuses on genetically engineered models that precisely recapitulate human pathogenic mutations;for the etiologically diverse DCM,this review systematically summarizes a full spectrum of models,including those induced by genetic defects,pharmaceutical/chemical factors,and hemodynamic stress.In addition,this review highlights the unique value of spontaneous large animal models,specifically the feline HCM model and the Boxer dog ACM model,in simulating the natural history of the disease,while also discussing the limitations and specific application scenari-os of each model category.