基于斑马鱼M-Act/Tox一体化评价的抗骨质疏松中药高效筛选思路与方法  

Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish

作　　者：王茉 凌洁 陈颖 宋捷[2,3] 孙娥 石子琪[2,3] 封亮 贾晓斌[2,3] 韦英杰 

机构地区：[1]解放军93318部队医院 [2]南京中医药大学第三临床医学院 [3]江苏省中医药研究院国家中医药管理局中药释药系统重点研究室

出　　处：《中国中药杂志》2017年第21期4246-4250,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81573833;81603500;81503253);国家"重大新药创制"科技重大专项(2017ZX 09301-056;2017ZX 09301-051);2015年度中医药行业科研专项(201507004-10);江苏省自然科学基金项目(BK20141507);江苏省六大人才高峰项目(2013-YY006)

摘　　要：日益显现的壮骨中药肝损伤问题为临床应用带来挑战,抗骨质疏松中药筛选有必要兼顾有效性与安全性,而代谢转化至关效应与毒性,故全面考虑代谢-效/毒一体的筛选具有意义。评价模型和化合物(含代谢物)数量严重制约早期在体、高效筛选。参考课题组前期相关研究及国内外文献,提出斑马鱼代谢模型、骨质疏松模型及毒性评价法有机整合可建立M-Act/Tox(metabolism-action/toxicity)一体化的抗骨质疏松中药高效筛选法。突破量微成分无法在体、高效及一体化评价的难点和盲点,实现基于体内过程且兼顾有效性与安全性的全方位抗骨质疏松中药高效筛选,对加速发现安全有效的抗骨质疏松创新中药具有意义。The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clin- ical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabol- ic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxic- ity （M-Act/Tox） for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds （in- cluding metabolites） severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad lit- erature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can＇t achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis.

关 键 词：斑马鱼 骨质疏松 药物代谢 有效性 安全性 活性筛选 

分 类 号：R285.5[医药卫生—中药学]