构建二肽基肽酶-Ⅳ抑制剂体外筛选模型及相关化合物抑制活性的测定  

Construction of Screening Model for Dipeptidyl Peptidase Ⅳ in vitro and Active Inhibitory Estimation of Related Compounds

作　　者：江慧贤[1] 罗超[2] 卢钧雄[1] 曹莹[1] 庞建新[1] 

机构地区：[1]南方医科大学药学院抗肿瘤药理学与新药评价,广州510515 [2]广州医学院第四附属医院药剂科,广州511400

出　　处：《中国实验方剂学杂志》2012年第4期210-215,共6页Chinese Journal of Experimental Traditional Medical Formulae

摘　　要：目的:建立二肽基肽酶-IV(DPP-IV)抑制剂体外筛选模型,并测定相关化合物的抑制率。方法:提取Caco-2细胞中DPP-IV,测定酶不同活力单位的吸光度(A),绘制活性-吸光度相关性曲线评价酶的活性与A的相关性;以sitagliptin为阳性对照测定其半抑制浓度(IC50)验证本实验模型;以该模型测定sitagliptin衍生物及对DPP-IV有抑制作用化合物的抑制活性。结果:酶的活性在一定范围内与A成直线相关;以本模型测定的sitagliptin IC50为18.354 nmol.L-1;JD-1,JD-2 IC50分别为3.4,2.6μmol.L-1,相关化合物的抑制率在21.45%～27.77%之间。结论:使用本DPP-IV抑制剂筛选模型测定的sitagliptin IC50与文献报道的相近,证明本模型的有效性,所测化合物有一定抑制活性。Objective：We aimed to establish a model to select dipeptidyl peptidase IV（DPP-IV）,and to test the inhibitory rate of the seven compounds.Method：DPP-IV was extracted from cultured Caco-2 cells and the values of absorbance（A） were tested in different activity units which were to evaluate the relation between the activity of DPP-IV and the value of A by the curve of activity-A.Sitagliptin as a positive control was used to evaluate the selected model.The derivatives from sitagliptin and the compounds were estimated inhibitory activity by the model.Result：The activity of DPP-IV was correlated to the value of A in a certain range.The IC50 values of sitagliptin,JD-1 and JD-2 were 18.354 nmol·L-1,3.4 μmol·L-1 and 2.6 μmol·L-1,respectively;the range of inhibitory activity for the compounds was between 21.45% and 27.77%.Conclusion：The IC50 of sitagliptin tested by this selected model is close to the value reported,which proves availability of the model.and meanwhile,the compounds estimated in this study contain inhibitory effect.

关 键 词：二肽基肽酶-IV抑制剂模型 半抑制浓度 抑制率 

分 类 号：R285.5[医药卫生—中药学]