化合物IMB-1680体外抗动脉粥样硬化的活性研究  

The in vitro anti-atherosclerotic activity of compound IMB-1680

作　　者：冯婷婷 李永臻 李霓 刘畅 王潇 许艳妮 司书毅 

机构地区：[1]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

出　　处：《药学学报》2014年第5期602-607,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81273515,81102443);国家“重大新药创制”科技重大专项资助项目(2012ZX09301002-001,2012ZX09301002-003);北京协和医学院“青年教师项目”(3332013089)

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(modified low density lipoprotein,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-1680在Sf9[hCD36]、CHO[hCD36]模型上IC50值分别为2.80及8.79μmol·L-1;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。In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti- atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9[hCD36] and CHO[hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC 50 of 2.80 and 8.79 gmol-L-l in sfg[hCD36] and CHO[hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce Dil-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.

关 键 词：IMB-1680 CD36 拮抗剂 动脉粥样硬化 高通量筛选 

分 类 号：R965.1[医药卫生—药理学]