重组aFGF乳酸菌的构建、表达及其对小鼠溃疡性结肠炎的药效研究  

Expression of Recombinant Human Acidic Fibroblast Growth Factor in Lactococcus lactic and the Therapy for Ulcerative Colitis in Mice

作　　者：仝雷[1] 张齐好[1,2] 邱壮伟[1] 苏志坚[1,2] 陈红霞[1] 黄亚东[1,2] 

机构地区：[1]暨南大学医药生物技术研究开发中心,广州510632 [2]暨南大学广东省生物工程药物重点实验室,广州510632

出　　处：《湖北农业科学》2011年第12期2508-2512,共5页Hubei Agricultural Sciences

基　　金：国家教育部新世纪人才计划(NCET-08-0611);国家重大新药创制项目(009ZX09103-749);广东省科技重点项目(2009B080701090)

摘　　要：采用分子克隆技术构建携带人酸性成纤维细胞生长因子(acidic fibroblast growth factors,aFGF)基因序列的乳酸菌重组表达载体pGMN4,转化并筛选出高效表达aFGF的重组菌株,制成活菌制剂。口服5%葡聚糖硫酸钠(DSS)溶液7d诱导小鼠溃疡性结肠炎(Ulcerative Colitis,UC),在造模同时分别给予高、中、低剂量活菌制剂灌胃17d。通过比较小鼠的毛色、体重、便血、结肠长度、病变组织的髓过氧化物酶(myeloperoxidase,MPO)活性,以及观察结肠组织病理形态学变化,验证重组aFGF乳酸菌对DSS诱导的小鼠UC的预防和治疗效果。实验结果表明,重组aFGF乳酸菌的表达量可达50μg/mL,高剂量重组活菌制剂能够显著改善小鼠的一般情况和溃疡导致的结肠缩短,促进组织修复,保持结肠结构的完整性,并下调MPO的活性。重组aFGF乳酸菌对小鼠UC具有良好的预防和治疗效果,将为UC治疗制剂的开发提供更加广阔的思路。Recombinant lactic acid bacteria vector pGMN4 containing human acidic fibroblast growth factor（aFGF） gene was constructed by molecular cloning techniques.Vector pGMN4 was transferred into Lactococcus lactic and the expression of aFGF was detected.Recombinant L.lactic was applied in the therapy for ulcerative colitis of mice induced by dextran sodium sulphate（DSS）.Recombinant L.lactic was used by stomach perfusion simultaneously with Ulcerative Colitis（UC） induction and continued for 17 d after the disease was induced.Some important parameters including general state of health,body weight,stool,colon length and the activity of myeloperoxidase（MPO） in ulcerated tissue were observed.The results showed that the expression of recombinant aFGF in lactic acid bacteria could be 50 μg/mL;high dosage of recombinant L.lactic could improve the general state of health,body weight,stool consistency,keep the integrity of colon,and lower the activity of MPO.Recombinant L.lactic could prevent the progression of UC,and would be a new biological therapeutic agent.

关 键 词：乳酸菌 人酸性成纤维细胞生长因子 溃疡性结肠炎 

分 类 号：Q815[生物学—生物工程]