论文部分内容阅读
为获得治疗类风湿关节炎(rheumatoid arthritis,RA)的先导药物,本研究比较了3种双特异性抗体(BsAB-1、BsAB-2和BsAB-3)对Ⅱ型胶原(CII)诱导的RA(CIA)模型小鼠的治疗效果。首先用ELISA法比较了3种二价抗体同时与两种抗原的结合能力,结果显示,3种抗体均能同时结合两种抗原,BsAB-1结合抗原的能力优于其他两种抗体(P<0.01)。用鸡CII建立CIA模型,用纯化的抗体对CIA模型小鼠进行治疗,每2天给药1次,治疗29天。治疗结束后与CIA模型对照组相比,各治疗组小鼠踝关节肿胀、皮肤紧绷、后足皮肤表面充血等临床症状明显减轻,其中BsAB-1治疗后足趾肿胀不明显,基本恢复正常。采用ELISA法检测了各组小鼠血清中CII抗体,real-time PCR法检测了脾脏中细胞因子IL-2、IL-1β、IL-17A和TNF-α的表达水平。与CIA模型对照组相比,所有抗体治疗组都能明显降低血清中CII抗体水平、脾脏中IL-2、IL-1β、IL-17A和TNF-α的表达量,且BsAB-1治疗效果最佳,与另外两种抗体比较有显著差异(P<0.01)。因此,3种二价抗体对CIA模型小鼠都有治疗效果,BsAB-1的治疗效果要优于另外两种抗体,是优选的先导药物。
In order to obtain a pilot drug for the treatment of rheumatoid arthritis (RA), we compared the effect of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) on type II collagen (CIA) model mice. Firstly, the binding ability of three kinds of bivalent antibodies to the two antigens was compared by ELISA. The results showed that all three antibodies could bind to two antigens at the same time. The ability of BsAB-1 to bind antigen was better than the other two antibodies (P < 0.01). The CIA model was established with chicken CII, CIA model mice were treated with the purified antibody and administered once every 2 days for 29 days. Compared with CIA model control group, the clinical symptoms of ankle joint swelling, tightness of the skin and hyperemia of the hindfoot skin were relieved in all the treatment groups after the treatment, in which the toe swelling was not obvious after BsAB-1 treatment and basically returned to normal . Serum CII antibody was detected by ELISA. The expression of cytokines IL-2, IL-1β, IL-17A and TNF-α in spleen were detected by real-time PCR. Compared with the CIA model control group, all the antibody treatment groups could significantly reduce the level of CII antibody in serum, the expression of IL-2, IL-1β, IL-17A and TNF-α in spleen, and the treatment effect of BsAB-1 Good, with the other two antibodies were significantly different (P <0.01). Therefore, the three bivalent antibodies have a therapeutic effect on CIA model mice, BsAB-1 treatment is superior to the other two antibodies, is the preferred lead drug.