抗体封闭趋化蛋白受体5对1型糖尿病发病的影响

Effects of anti-chemokine receptor-5 antibody on type 1 diabetes

目的 :研究体内封闭趋化蛋白受体 5 (CCR5 )分子对严重联合免疫缺陷小鼠 (severe combined im munodeficientNOD,NOD.Scid) 1型糖尿病发病的影响。 方法 :将发病非肥胖性糖尿病小鼠 (1只 )的脾细胞腹腔注射至 NOD.Scid小鼠体内 ,将这些小鼠随机分成 2组 (每组 8只 ) :抗 CCR5组小鼠腹腔注射抗 CCR5膜外第一襻的多克隆抗体 ,1周 3次 ,共计 12次 ;对照组相同方法注射 PBS,同时测定其血糖和体重。脾细胞注射后 70 d或当小鼠出现重度糖尿病临床表现时处死 ,进行组织学观察和脾细胞分泌细胞因子的 EL ISA测定。 结果 :脾细胞射后 70 d内 ,抗 CCR5组小鼠糖尿病发病率为 37.5 % (3/ 8) ,对照组为 10 0 % (8/ 8) ;胰腺炎积分抗 CCR5组较对照组差异显著 (P<0 .0 5 ) ;抗 CCR5组 IL- 2、IL- 10、IFN- γ水平分别为 2 5 .2、2 7.3pg/ ml和 0 .2 38ng/ ml,对照组为 5 7.7、31.6 pg/ ml和 18.0 3ng/ ml,前者的 IL- 2和 IFN- γ水平显著低于后者 (P<0 .0 5 )。结论 :在 NOD.Scid小鼠体内注射抗体封闭 CCR5可以部分抑制 1型糖尿病的发生。

Objective:To explore the anti-diabetogenic effect of antibody blocking portion of chemokine receptor-5 antibody(CCR5) molecule.Methods: The severe combined immunodeficient NOD(NOD.Scid) mice,injected i.p.with splenocytes from nonobese diabetic mouse,were randomly divided into 2 groups(8 of each group): anti-CCR5 Ab group and PBS group.The mice in anti-CCR5 Ab group were treated with a specific polyclonal antibody,targeting the first extracellular loop of CCR5,and PBS group was treated with PBS.Blood glucose levels were measured to observe the anti-diabetogenic effect of the antibody.Histological examination and ELISA analysis were also performed.Results: Within 70 d,all of the control mice developed diabetes while 5 of the 8 mice treated with anti-CCR5 Ab were diabetes-free.The difference of inflammation score between 2 groups was significant(P<0.05).The supernatant of cultured splenocytes from anti-CCR5-treated mice contained IL-2(25.2 pg/ml),IL-10(27.3 pg/ml) and IFN-γ(0.238 ng/ml), whereas that from control mice contained IL-2(57.7 pg/ml),IL-10(31.6 pg/ml) and IFN-γ(18.03 ng/ml).Conclusion: Administration of antibody,which targeting the first extracellular loop of CCR5,can induce the resistance to type 1 diabetes in the adoptive transfer model.