筛选糖尿病候选药物FGF-21受体激动剂的新型细胞模型的建立  

Establishment of a novel cell model targeted on FGF-21 receptor for screening anti-diabetic drug candidates

作　　者：高红梅[1] 王文飞[1] 张巧[1] 韩阳[1] 王琪[1] 任桂萍[1] 付云威[2] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院 [2]东北农业大学医院,黑龙江哈尔滨150030

出　　处：《药学学报》2011年第8期904-909,共6页Acta Pharmaceutica Sinica

基　　金：黑龙江省科技厅重点攻关项目(2006G0461-00);黑龙江省博士后科研启动资助金资助;黑龙江省教育厅项目(11521022)

摘　　要：建立以成纤维细胞生长因子-21(fibroblast growth factor-21,FGF-21)信号通路为靶点的药物筛选细胞模型,用于筛选FGF-21受体激动剂类的新型治疗糖尿病药物。FGF-21的生理功能主要是通过细胞表面的FGFR及辅助受体βklotho传递信号,从而激活细胞内相关调控的一系列信号通路以及基因转录来实现的。本实验将βklotho基因构建到逆转录病毒表达载体pBMN-IRES-EGFP。将该载体导入包装细胞,收集病毒上清液并感染3T3-L1细胞,筛选到稳定表达βklotho细胞系。该细胞模型在FGF-21作用下可以促进细胞葡萄糖转运蛋白-1表达及转运水平升高,从而提高细胞糖吸收能力。构建该细胞系可以方便对FGF-21及类似药物进行高通量筛选,为糖尿病药物的研究提供了一种新方法。The aim of this project is to establish a fibroblast growth factor-21（FGF-21） signaling pathway targeted cell model,for screening a class of FGF-21 receptor agonists as anti-diabetic candidates.FGF-21 requires β klotho transmembrane proteins as co-receptor for the activation of tyrosine kinase FGF receptor（FGFR） signaling,thereby activating a series of intracellular signaling pathways and regulating gene transcription for glucose metabolism.Firstly a recombinant plasmid expressing co-receptor β klotho and EGFP reporter genes was constructed.After introducing the recombinant plasmid into package cells,the cell culture supernatant was used to infect 3T3-L1 cells,which were then screened for stably expressing β klotho gene.Administration of FGF-21 increased the expression of GLUT1 and stimulated GLUT1-mediated glucose uptake.This novel cell model can be conveniently used in high-throughput drug screening of FGF-21 or FGF-21 analogues.

关 键 词：FGF-21 βklotho 药物筛选 糖尿病药物 

分 类 号：R965.1[医药卫生—药理学]