FGF21-L-Fc融合蛋白表达及其降糖作用初步评价  

Expression and pharmacological evaluation of fusion protein FGF21-L-Fc

作　　者：姚文兵[1] 任桂萍[1] 韩阳[1] 曹宏伟[2] 高红梅[1] 阚方明[1] 王琪[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院,黑龙江哈尔滨150030 [2]黑龙江八一农垦大学生命科学技术学院,黑龙江大庆163319

出　　处：《药学学报》2011年第7期787-792,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：成纤维细胞生长因子-21(FGF21)是FGF家族成员之一,最近发现具有独立调节血糖的作用。为了提高FGF21稳定性来达到更好的药效,通过柔性接头连接,制备重组融合蛋白FGF21-L-Fc,并对其生物学活性和体内药效学进行初步研究。纯化后的FGF21-L-Fc融合蛋白经鉴定,其分子量和特异性均与理论值相符。经微量化的GOD-POD法检测表明,FGF21-L-Fc融合蛋白能刺激体外培养的已分化成熟的3T3-L1脂肪细胞葡萄糖吸收,其葡萄糖消耗率与野生型相比有很大提高;在STZ造模糖尿病小鼠体内,其药效比野生型持续时间长。结果表明,改造的蛋白比野生型药效更持久,为以后FGF21的临床应用奠定了基础。FGF21（fibroblast growth factor 21） is a recently described member of the FGF family.It has been previously demonstrated that FGF21 is a potent regulator of glucose homeostasis.To improve stability of FGF21 for better efficacy,a new form of recombinant FGF21 was generated by fusion of a full length FGF21 gene and the Fc fragment of human IgG4 with flexible linker sequence.To examine the glucose regulation activity of FGF21-L-Fc,3T3-L1 pre-adipocytes were differentiated into adipocytes,and glucose uptake activity of FGF21-L-Fc was examined by glucose oxidase and peroxidase（GOD-POD） assay.The results showed that in comparison with wild type FGF21,FGF21-L-Fc was more potent in stimulation of glucose uptake by 3T3-L1.In vivo studies on the modified protein demonstrated that FGF-L-Fc had a better efficacy in lowering blood glucose of the STZ-induced diabetic animals and controlled glucose level for a longer time.The results provided a sound basis for further studies.

关 键 词：FGF21-L-Fc 葡萄糖吸收 稳定性 

分 类 号：R963[医药卫生—微生物与生化药学]