重组人胰岛素样生长因子-1局部毒性、免疫原性研究

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7 d皮下注射rhIGF-1，末次给药后48 h ，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14 d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-12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。

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

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 .