化合物IMB-1680体外抗动脉粥样硬化的活性研究.pdfVIP

·602 · 药学学报 ActaPharmaceuticaSinica2014，49(5)：602—607 化合物 IMB．1680体外抗动脉粥样硬化的活性研究 冯婷婷，李永臻，李 霓，刘 畅，王 潇，许艳妮 ，司书毅 (中国医学科学院、北京协和医学院医药生物技术研究所国家新药 (微生物)筛选实验室，北京 100050) 摘要：探讨化合物 IMB．1680的体外抗动脉粥样硬化活性。利用已构建的高表达人CD36细胞株 Sf9[hCD36] 和 CHO[hCD36]测定量效曲线，荧光显微照相法和流式细胞实验检测细胞对变性低密度脂蛋 白 (modifiedlow densitylipoprotein，mLDL)的摄取，巨噬细胞泡沫化实验检测细胞 内脂质积 聚。结果表 明：IMB一1680在 Sf9[hCD36]、CHO[hCD361模型上Ic如值分别为2．80及8．79pmol·L ；IMB．1680能显著抑制细胞摄取DiI．AcLDL， 同时能显著减少巨噬细胞 RAW264．7摄取脂质。本研究为开发新型抗动脉粥样硬化药物奠定了基础。 关键词：IMB一1680；CD36；拮抗剂：动脉粥样硬化；高通量筛选 中图分类号：R965．1 文献标识码：A 文章编号：0513—4870(2014)05—0602—06 Theinvitroanti-atheroscleroticactivityofcompoundIM B-1680 FENG Ting．ting，LIYong．zhen，LINi，LIU Chang，WANGXiao，XU Yan—ni，SIShu—yi (NationalCenterfo，Drug(Microbiology)ScreeningLaboratory,InstituteofMedicinalBiotechnology ChineseAcademyofMedicalSciences＆PekingUnionMedicalCollege,Bejiing100050,China、 Abstract：Inthepreviousstudy,ahigh-throughputscreeningmethodwasestablishedtofindtheantagonists OfCD36． Inthepresentstudy,anew compoundnamedIMB一1680wasfoundusing thismethod． Theanti— atheroscleroticactivitiesofIMB一1680 werethen evaluated． Dose．dependentactivitiesofIMB．1680 were detectedbyusingSf9[hCD36]andCHO[hCD36]models．Fluorescencemicroscopicphotographyandflow cytometrywereusedtoanalyzeuptakeofmLDL． Foam celltestwithRAW 264．7macrophageswasusedto examinelipidaccumulation． TheresultsshowedthatIMB一1680inhibitedCD36activitywithIC nof2．80and 8．79pmolL‘ inSf9[hCD36]andCHO[hCD36]cells，respectively．Fluorescencemicroscopicphotographyand flow cytometryrevealedthatIMB．1680couldsignificantlyreduceDil—AcLDLuptake． Meanwhile．IMB．1680 alsocouldreducelipidsaccumulation inRAW 264．7macrophages． Inal1．thedataindicatedthatIMB．1680 mightbeapotenteffectiveanti．atherOsclerOticleadingcompound． Keywords：IM B一1680；CD36；antagoni