胰升糖素样肽1类似物利拉鲁肽对正常人和1型糖尿病患者CD4＋CD25-T细胞增殖的影响  

Role of glucagon-like peptide-1 analogue liraglutide played in the proliferation of CD4＋ CD25- T cells in normal people and type 1 diabetic patients in vitro

作　　者：胡瑛[1] 苏欣[1] 刘灵佳[1] 向宇飞[1] 余琪琪[1] 易受南[1] 周智广[1] 

机构地区：[1]中南大学湘雅二医院内分泌科,中南大学糖尿病中心,中南大学代谢内分泌研究所,糖尿病免疫学教育部重点实验室,长沙410011

出　　处：《中华内分泌代谢杂志》2013年第6期474-478,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：湖南省自然科学基金资助项目（11JJ7005）;教育部长江学者和创新团队发展计划资助（IRT1195）：诺和诺德β-cellAcademy保健专项资金项目

摘　　要：目的观察胰升糖素样肽1（GLP—1）类似物利拉鲁肽对正常人和新发1型糖尿病患者外周皿CD4＋CD25-T细胞增殖的影响，评价利拉鲁肽对1型糖尿病可能的免疫调节作用。方法免疫磁珠法分离10名正常人和10例新发1型糖尿病患者的外周血CD4＋CD25T细胞．用CD3／CD28单抗包被的T细胞扩增磁珠刺激增殖。以CFSE染色通过流式细胞术比较在不同浓度利拉鲁肽（0、25、50和100nmol／ml）干预后，对CD4＋CD25＋T细胞增殖的影响。结果（1）利拉鲁肽剂量依赖性抑制正常人和新发1型糖尿病患者的CD4＋CD25＋T细胞的增殖（各干预浓度组间P〈0．05）；（2）在利拉鲁肽各干预浓度组，1型糖尿病患者的CD4＋CD25T细胞的增殖作用显著强于正常人的CD4＋CD25T细胞（P〈0．01）：（3）利拉鲁肽对正常人和新发1型糖尿病患者的CD4＋CD25T细胞增殖的抑制程度则无明显差别（P〉0．05）。结论1型糖尿病患者的CD4＋CD25＋T细胞的增殖作用显著增强，提示1型糖尿病患者存在细胞免疫紊乱。利拉鲁肽在体外对CD4＋CD25-T细胞的增殖具有抑制作用，这种免疫负性调节作用使其在1型糖尿病治疗方面具有潜在的应用价值，Objective To study the role of glucagon-like peptlde-1 （ GLP-I ） analogue liraglutide played in the proliferation of CD4＋ CD25- T cells in normal people and newly-onset type 1 diabetie patients, and to evaluate the possible immune regulatory role of liraglutide in the therapy of type 1 diabetes. Methods CD4＋ CD25 T cells of 10 normal people and 10 newly-onset type I diabetic patients were separated from peripheral blood by MACS immunomagnetie beads and stimulated by Human T-Activator CD3/CD28 Dynabeads to proliferate. CFSE labeling teehnique was used to evaluate the proliferation of CD4＋ CD25 T cells by flow eytometry. Liraglutide of different eoncentrations（0, 25,50, and 100 nmol/ml） was added to the proliferation system, then the proliferation of CD4＋ CD25 T cell was measured. Results （ 1 ） Liraglutide suppressed the proliferation of CD4＋CD25 T cells from either normal people or type 1 diabetic patients with dose-dependent manner （P 〈 0. 05 ）. （2） Under the difterent concentrations of liraglutide, the proliferation of CD4＋ CD25- T cells fl＇om diabetic patients was much more robust than that of normal people （ P〈0.01 ）. （ 3 ） The inhibitory effects of liraglutide on CD4＋ CD25 T cells proliferation in normal people and diabetic patients were similar （ P〉0.05 ）. Conclusion The proliferation of CD4＋ CD25 T cells in type 1 diabetic patients was more robust than normal people, which indicated cellular immune dysfunction in type 1 diabetes. Liraglulide inhibits the proliferation of CD4＋ CD25 T cells of type 1 diabetic patients in vitro. The immunosuppression effect of liraglutide may have potential value in the treatment of type 1 diabetes.

关 键 词：胰升糖素样肽1 利拉鲁肽 CD4+CD25+ T细胞 免疫调节 

分 类 号：R587.1[医药卫生—内分泌]