基于斑马鱼MActTox一体化评价抗骨质疏松中药高效筛选思路与方法.docVIP

基于斑马鱼MActTox一体化评价抗骨质疏松中药高效筛选思路与方法 　　[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MAct/Tox（metabolismaction/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。 　　[关键词]斑马鱼； 骨质疏松； 药物代谢； 有效性； 安全性； 活性筛选 　　[Abstract]The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application， and it is necessary to consider both effectiveness and safety in screening antiosteoporosis Chinese medicines Metabolic transformation is closely related to drug efficacy and toxicity， so it is significant to comprehensively consider metabolismaction/toxicity（MAct/Tox） for screening antiosteoporosis Chinese medicines The current evaluation models and the number of compounds（including metabolites） severely restrict efficient screening in vivo By referring to previous relevant research and domestic and abroad literature， zebrafish MAct/Tox integrative method was put forward for efficiently screening antiosteoporosis 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 antiosteoporosis 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. 　　[Key words]zebrafish； osteoporosis； metabolism； effectiveness； safety； activity screening 　　中药治疗骨质疏松症受到青睐，但其肝毒性也已引起重视，有些疗效确切、临床用药广、关注度高的知名中药如壮骨关节丸、仙灵骨葆胶囊（《2012版中国国家基本药物目录》在列唯一补肾壮骨中成药）等有肝脏不良反应，且均已在《药品不良反应信息通报》公开，这对临床安全、合理用药带来极大挑战[13]。故抗骨质疏松中药筛选有必要既重视有效性，又重视安全性。中药的效应（action，Act）/