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作 者:李瑞红 柳娟 孙旭尔 王韫芳 Ruihong Li;Juan Liu;Xuer Sun;Yunfang Wang(Bejing Tsinghua Changgung Hospital,Tsinghua University,Bejing,102218;Institue of Health Service and Transfision Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
机构地区:[1]清华大学附属北京清华长庚医院,北京102218 [2]军事科学院军事医学研究院卫生勤务与血液研究所,北京100850
出 处:《生命科学仪器》2020年第4期41-52,共12页Life Science Instruments
基 金:国家科技重大专项(2017ZX100203205)。
摘 要:药物的生物安全性是决定新药研发成败的第一要素,肝脏是药物毒性的主要靶点,开发高效、可靠、便捷、安全的药物肝毒性预测模型是制药领域重点关注的难点和热点。良好的体外毒性预测模型需要选择适宜的细胞种类及完善的培养体系,以维持细胞的肝脏特异性功能。随着技术的革新,各种药物肝毒性评价模型应运而生,然而,受限于离体与在体环境的固有差异,任何模型都有其优势和局限性,只能通过不断优化模型体系,或针对性的选择特定的模型,才能获得更为准确的评价结果。本文综述了体外药物肝毒性预测模型的研究现状,涉及主流的体外模型的构建方法、特点属性、改良方案及应用前景,希望能为肝毒性研究提供一些新的思路。Biological safety is the first factor to determine the successful development of a new drug.Since the liver is the main target of drug toxicity,the development of efficient,reliable,convenient and safe drug hepatotoxicity prediction models is a difficulty and hot spot in the pharmaceutical field.A good in vitro toxicity prediction model requires selection of appropriate cell types and a complete culture system to maintain the liver-specific functions of the cells.With technological innovation,various drug hepatotoxicity evaluation models have emerged.However,due to the inherent differences between the in vitro and in vivo environments,any model has its advantages and limitations.In order to get more accurate evaluation results,the model ought to be continuously optimized and an appropriate kind of model should be selected when in need.This article reviews the current research status of in vitro drug hepatotoxicity prediction models,involving construction methods,characteristics,optimizations and prospects of mainstream in vitro model,hoping to provide some new ideas for hepatotoxicity research.
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