新型疫苗肽IA-2-P2对1型糖尿病的治疗作用  

Vaccination against Type 1 Diabetes with a Novel Peptide IA-2-P2

作　　者：吴洁[1] 申丽丽[1] 黄东成[1] 金亮[1] 李国梁[1] 刘坤锋[1] 杨雪[1] 刘晓锐[1] 

机构地区：[1]中国药科大学生命科学与技术学院微基因药物实验室,江苏南京210009

出　　处：《药物生物技术》2014年第4期293-296,共4页Pharmaceutical Biotechnology

基　　金：国家自然科学基金资助项目(No.81172973;31270985)

摘　　要：IA-2-P2是由来自P277多肽的T表位与胰岛素瘤相关蛋白2(IA-2)的B表位组合而成的新疫苗肽,为验证其对1型糖尿病的治疗效果,采用多次小剂量注射链脲佐菌素(STZ)诱导C57BL/6雄性小鼠建立1型糖尿病模型,成模2 w后,sc 100μg多肽进行免疫治疗,间隔3 w免疫,共6次,每3 w收集被免疫动物的血清进行生化分析,测定血糖浓度和IgG抗体滴度并进行体重监测。结果显示IA-2-P2多肽能在一定程度上降低血糖,与对照组相比,IA-2-P2组终末平均血糖下降38%;并能维持小鼠的体重的稳定;多肽治疗能延长小鼠生存时间,在32 w观测期间,IA-2-P2组小鼠生存率达70%,较对照组40%的生存率有显著差异(P<0.05);并且具有免疫调节作用,ELISA结果显示多肽可以有效引起免疫应答产生,与对照组相比,抗体水平有显著差异(P<0.05)。IA-2-P2 is a novel peptide derived from P277 and combined with a fragment of islet cell antigen（ IA-2）. The aim of our study was to manifest its efficacy in type 1 diabetic mouse model established by intraperitoneal injection of multiple low dose streptozotocin（ MLD-STZ） in male C57 BL /6 mice. Diabetic mice in treatment group received administration of 100 μg of peptide in mineral oil given six times subcutaneously after STZ toxin induction at 3-week intervals. Blood serum was collected for biochemical analysis every two weeks,including blood glucose test and measurement of antibody titer. Body weight of mice was also one of the endpoint to evaluate the pharmacodynamics effect. The results showed that peptide IA-2-P2 treated mice had lower blood glucose level compared with control group（ reduced by 38%）,which indicated that the peptide IA-2-P2 could make a good performance on glucose control in some degree. It also maintained the body weight normal. In addition,treatment with peptide could increase the survival rate of diabetic mice. At the end of observation period of 32 weeks,70% of mice in IA-2-P2 treated group were still alive,while the survival rate in control group was only 40%. The peptide also led to an immune response. ELISA results demonstrated that peptides treated groups had an increasing tendency in IgG antibody titer after every administration and the changes were remarkable（P〈0. 05）.

关 键 词：1型糖尿病 链脲佐菌素 疫苗 血糖 免疫 抗体 

分 类 号：Q516[生物学—生物化学] R587.1[医药卫生—内分泌]