scBsAb1/17双特异性抗体对小鼠类风湿性关节炎模型的治疗效果  

Therapeutic effect of scBsAb1/17 on rheumatoid arthritis mice models

作　　者：齐剑英[1] 郭茉[1] 叶贤龙[1] 阚方明[1] 张宇[1] 郝智超[1] 徐黎明 任桂萍[1] 王文飞[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院生物制药教研室,黑龙江哈尔滨150030 [2]中国水产研究院黑龙江水产研究所,黑龙江哈尔滨150030

出　　处：《中国药理学通报》2013年第3期366-371,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 201031001084);哈尔滨市科技创新人才研究专项资金(No 2008RFQXS017);东北农业大学生物学理科基地科研训练及科研能力提高项目子项目(No J1210069)

摘　　要：目的比较不同剂量scBsAb1/17对Ⅱ型胶原(CII)诱导类风湿性关节炎(CIA)模型小鼠的治疗效果,及scBsAb1/17双特异性抗体与单价抗体(anti-IL-1βscFv和anti-IL-17scFv)在CIA模型小鼠中的治疗效果。方法利用CII建立小鼠类风湿性关节炎模型,小鼠成模后开始治疗,每2 d给药1次,治疗29 d。治疗结束后对小鼠关节炎指数进行临床评分,检测各组小鼠血清中CII抗体、CII特异性刺激的脾细胞增殖指数和脾脏中IL-2、IL-1β、IFN-γ、IL-6和TNF-α等细胞因子的表达水平。结果与CIA模型对照组相比,所有治疗组都能明显减轻CIA小鼠的临床症状,并明显降低血清中CII抗体水平、脾细胞增殖指数及脾脏中TNF-α、IL-6、IL-2、IL-1β和IFN-γ的表达量。相同剂量下scBsAb1/17治疗组的脾细胞增殖指数明显低于anti-IL-1βscFv治疗组(P<0.05);并且scBsAb1/17治疗组小鼠脾脏中IL-6、IL-2、IL-1β和IFN-γ的表达量明显低于anti-IL-1βscFv和anti-IL-17AscFv单独治疗组(P<0.01或P<0.05)。结论 scBsAb1/17及单价抗体对CIA模型小鼠都有治疗效果;不同剂量scBsAb1/17对CIA模型鼠的治疗效果呈剂量依赖性;相同剂量条件下,scBsAb1/17的治疗效果要优于单价抗体。Aim To detect the therapeutic effect of the different doses of scBsAb1/17 in CIA model mice,and compare the treatment effect of the same dose of scBsAb1/17 with the monovalent antibody（anti-IL-1β scFv and anti-IL-17 scFv） in CIA model mice.Methods CIA models of mice were established.When the clinical symptoms became obvious,the mice were treated by antibodies every two days,and clinical arthritis index was scored.On the 29th day after the treatment,CII antibody level in serum of each group,the spleen cell proliferation index after stimulation by CII,and the cytokine expression in the spleen were tested.Results Compared with the CIA model mice,treatment with antibodies significantly alleviated the clinical symptoms of the CIA model mice,and decreased the CII antibody in serum,stimuli index of splenocytes and production of TNF-ɑ,IL-6,IL-2,IL-1β and IFN-γ.scBsAb1/17 was more potent in inhibition of collagen-specific proliferation of splenocytes compared with anti-IL-1β scFv and anti-IL-17A scFv treatment group.scBsAb1/17 more effectively inhibited mRNA expression of IL-6,IL-2,IL-1β and IFN-γ in the spleen of CIA model mice than the anti-IL-1β scFv and anti-IL-17A scFv.Conclusion Both scBsAb1/17 and monovalent antibodies have treatment effect on CIA model mice;the different doses of scBsAb1/17 mouse model of CIA treatment effect are in a dose-dependent manner;scBsAb1/17 at the same dose has a better therapeutic efficacy than the monovalent antibody.

关 键 词：双特异抗体 单价抗体 类风湿性关节炎(RA) Ⅱ型胶原(CII) IL-1Β IL-17A 

分 类 号：R-332[医药卫生] R392.11