新型动物和非动物药物心脏安全性评价模型  

Novel animal and non-animal cardiac safety evaluation models

作　　者：温正超 张可娇 许金城 蒋雅楠 WEN Zheng-chao;ZHANG Ke-jiao;XU Jin-cheng;JIANG Ya-nan(Department of Pharmacology,College of Pharmacy,Harbin Medical University,Harbin HEILONGJIANG 150081,China;Translational Medicine Research and Cooperation Center of Northern China,Heilongjiang Academy of Medical Sciences,Harbin HEILONGJIANG 150086,China)

机构地区：[1]哈尔滨医科大学药学院药理学教研室,黑龙江哈尔滨150081 [2]黑龙江省医学科学院北方转化医学研究合作中心,黑龙江哈尔滨150086

出　　处：《中国新药与临床杂志》2024年第5期333-338,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金(82370269);黑龙江省自然科学基金(LH2021H018);黑龙江省博士后科学基金(LBH-Q21134)。

摘　　要：药物诱导的心脏毒性是药物研发失败的重要原因之一,亟需建立方法早期筛查新药对心脏的影响。但是,传统药物心脏安全性评价模型已不能满足药物研发的需求。因此,开发高效、廉价的药物心脏安全性的评价和机制研究模型对新药研发和药物的临床合理应用至关重要。近年来,除传统动物模型外,斑马鱼、果蝇、秀丽隐杆线虫等也被用于药物毒性研究。基于转基因技术可以建立基因表达谱和调节方式与人类相似的人源化动物模型,这类模型的开发和应用有助于解决药物研究中的种属差异问题。此外,器官芯片、类器官、网络毒理学等非动物方法也相继被开发。新型药物心脏安全性评价模型有助于药物心脏毒性防治及药物开发。Drug-induced cardiotoxicity is one of the important reasons for the failure of drug development,and it is urgent to establish methods to screen the impact of drugs on the heart in the early stage.However,the traditional drug safety evaluation models are unable to meet the requirements of drug development.Therefore,the development of efficient and inexpensive drug safety evaluation and mechanism study models are very important for the development of new drugs and rational clinical application of drugs.In recent years,in addition to traditional animal models,the zebrafish,Drosophila,and Caenorhabditis elegans have been used for drug safety research.Based on transgenic technology,humanized animal models with gene expression profiles and regulation similar to that of humans can be established,and the development and application of such models can be used to solve the problem of species differences in drug research.In addition,nonanimal methods such as organ chips,organoids,and network toxicology have also been developed.The novel cardiac safety evaluation models would be helpful for drug cardiotoxicity prevention and treatment,as well as drug development.

关 键 词：心脏毒性 药物评价 临床前 模型 动物 类器官 

分 类 号：R965.3[医药卫生—药理学]