心肌细胞损伤的体外模型研究新进展

Research progress on in vitro models of cardiomyocyte injury

心血管疾病严重危害人类生命健康,其中伴随的心肌损伤越来越受到社会各界的重点关注。中药作为我国新药研发的天然宝贵资源,其多组分、多途径、多靶点的特征已在抗心肌损伤方面显示出独特的优势。近年来,随着离体心肌细胞培养技术的广泛应用,成本经济、环境可控、样本均一的心肌细胞损伤模型,逐渐成为研究心肌细胞药理损伤作用机制以及开发相关抗损伤药物的重要方法之一。一个合理的体外模型不仅能减少经济投入、有效防止人力耗散,又能准确反映实验机制,更理想地模拟临床变化过程,故筛选和构建损伤模型是研究的关键和核心。该文根据临床病症的不同将模型分类,总结了心肌细胞缺氧-复氧损伤、肥大损伤、氧化应激损伤、炎症损伤、内环境紊乱以及毒性损伤等十余种模型的建模原理、评价指标和应用案例,并分析归纳其相应的优点与技术难点,以期为心肌损伤机制深入研究,及相应的药物研发提供有益的参考。

Cardiovascular diseases seriously endanger human health and life.The accompanying myocardial injury has been a focus of attention in society.Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics.In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism.Therefore,the selection and establishment of in vitro model are crucial for the in-depth research.This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity.Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.