中国药理学通报2017,Vol.33Issue(3):327-334,8.DOI:10.3969/j.issn.1001-1978.2017.03.008
抗肾纤维化药物高内涵筛选模型的建立及应用
Establishment and application of high content screening model for anti-renal fibrosisdrugs
摘要
Abstract
Aim Toestablishacellularmodelofrenal fibrosis in vitro,which can be used for the high-content analysis,and lay a good foundation for the screening and mechanism study of traditional Chinese medicine compoundswithanti-fibroticeffect.Methods Inthis study,normal rat kidney fibroblasts(NRK49F)were induced by TGF-β1 .As the maker ofmyofibroblast,al-pha smooth muscle actin (α-SMA)was detected andanalyzed by high content imaging analysis system,and the cell plate density,induction time,the concentra-tion of serum in medium were optimized,to establish a stable model of renal fibrosis in vitro.Then the model was validated by TGF-β1 receptor blocker SB525334, curcumin and emodin.On this basis,whether pirfeni-done had the effect of anti-renal fibrosis was explored. Results Byoptimizingthecelldensity,inductiontime and serum concentration in culture medium,the conditions of NRK49 F renal fibrosis model in vitro for high content analysis were established. SB525334, curcumin and emodin and pirfenidone reduced the ex-pression of α-SMA in NRK49 F induced by TGF-β1 . Conclusions Aninvitromodelofrenalfibrosis, which can be used for high content screening technolo-gy,is established and can be used to screen drugs withanti-renal fibrosis effects relatively stably.Pirfenidone in this model inhibits the transformation of NRK49 F in-to myofibroblasts,suggesting that it may be able to in-hibit renal fibrosis,providing a way for the selection of objects for anti-renal fibrosis drug screening.关键词
肾纤维化/细胞模型/高内涵分析技术/NRK49F/α-SMA/中药化合物Key words
renal fibrosis/cell model/high-content a-nalysis/NRK49 F/α-SMA/Chinese traditional medicine compounds分类
医药卫生引用本文复制引用
孙雪娇,刘祎,李城,王曦廷,吴清华,张宇欣,栗世铀,李亚东,李彧..抗肾纤维化药物高内涵筛选模型的建立及应用[J].中国药理学通报,2017,33(3):327-334,8.基金项目
国家自然科学基金面上项目(No 81573716,No 81173642) (No 81573716,No 81173642)