重组人胰岛素样生长因子-1局部毒性、免疫原性研究  

Studies on Local Toxicity and Immunogenicity of Recombinant Human Insulin-like Growth Factor-1

作　　者：张水华[1,2] 陈芯媛 杨渐[1] 叶丽香[2] 林经东[2] 辛志明[2] 林菁[2] 俞昌喜[1,2] 

机构地区：[1]福建医科大学药学院药理学系,福州350108 [2]福建医科大学福建省新药安全性评价中心,福州350108

出　　处：《福建医科大学学报》2014年第3期174-177,182,共5页Journal of Fujian Medical University

基　　金：福建省高校产学合作科技重大项目(2010Y4002);福建医科大学博士科研启动基金(2011BS002)

摘　　要：目的考察重组人胰岛素样生长因子-1(rhIGF-1)的局部毒性、免疫原性。方法家兔连续7d皮下注射rhIGF-1,末次给药后48h,对给药部位皮肤进行组织病理学检查;豚鼠隔日连续3次腹腔注射rhIGF-1致敏,末次致敏后14d静脉注射激发,激发后密切观察过敏反应症状;体外试管法观察rhIGF-1的溶血作用;小鼠每周皮下注射rhIGF-1 2次,连续4周,间接ELISA法检测抗体产生情况。结果皮下刺激性试验提示,rhIGF-1对皮下组织有刺激作用;全身主动过敏反应中阴性对照组过敏反应呈阴性,低剂量组、高剂量组和阳性对照组过敏反应呈极强阳性;体外溶血试验不引起溶血反应;间接ELISA结果表明,给药1周,未见动物产生抗体,从给药2周开始,所有动物均产生抗体,且随着给药时间的延长,抗体滴度明显上升。结论 rhIGF-1对动物具有致敏性、刺激性、免疫原性,但不引起溶血反应。Objective To explore local toxicity and immunogenicity of recombinant human insulin-like grow th factor-1 （rhIGF-1） . Methods rhIGF-1 was injected subcutaneously in rabbits for continuous 7 days . At 48 h after the last administration ,histopathology of subcutis at injection site was examined . rhIGF-1 was injected intraperitoneally in guinea pigs every other day for 3 times to sensitize the animals and rhIGF-1 with double doses was injected to challenge in the 14 days after the last sensitization . The symptom of anaphylaxis was closely observed after challenging . The hemocytolysis of rhIGF-1 was ob-served by means of test tube method . rhIGF-1 was injected subcutaneously in mice twice a week for 4 weeks ,then antibody was detected by indirect ELISA . Results Subcutaneous irritation test showed that rhIGF-1 had a stimulating effect on the subcutis . Active systemic anaphylaxis was extremely positive ex-cept that of the negative group . In vitro hemolysis test did not show any hemolytic reaction . The result of indirect ELISA showed that no antibody was detected by the first week of the study and all animals de-veloped antibody after the second week of the study . As the dosing time lasted ,the antibody titers in-creased significantly . Conclusions rhIGF-1 has sensitization ,stimulation and immunogenicity ,but no hemolytic activity .

关 键 词：胰岛素样生长因子-1 重组蛋白质类 皮肤试验 过敏反应 溶血 溶血性斑块技术 疾病模型  动物 

分 类 号：R3411[医药卫生—基础医学]