CCL20单克隆抗体与雷公藤治疗胶原诱导性关节炎模型小鼠的对照研究

目的 研究趋化因子CCL20在胶原诱导性关节炎(collagen-induced arthritis,CIA)小鼠中的表达,探讨CCL20单克隆抗体对CIA小鼠的治疗作用及临床治疗类风湿关节的潜在价值.方法 ①建立CIA小鼠模型:40只DBA/1小鼠随机分为健康对照组、模型组、CCL20单克隆抗体治疗组、雷公藤治疗组；②观察不同时间点小鼠一般情况、关节肿胀度；③测定造模42天后小鼠血清CCL20、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)的表达水平；④观察各组小鼠关节病理变化.结果 ①模型组、雷公藤组和单抗组CCL20,TNF-α和IL-1β均高于对照组,CCL20(29.45±4.92) ng/L、(18.32±4.80) ng/L、(14.13±3.82) ng/L vs (2.83±1.37) ng/L;TNF-α(63.1±2.82) ng/L、(43.15±2.31) ng/L、(42.91±2.02) ng/L vs (26.78±3.50) ng/L;IL-1β(83.72±4.04) ng/L、(53.78±5.89) ng/L、(56.77±4.98)ng/L vs(16.54±2.45)ng/L,雷公藤组和单抗组的CCL20、TNF-α和IL-1β均低于模型组.②HE染色观察,模型组较正常组滑膜肥厚,排列紊乱、滑膜内有大量炎症细胞浸润,有血管翳形成.雷公藤组和单抗组较模型组明显减轻.结论 CCL20在CIA小鼠中异常高表达,以CCL20单克隆抗体阻断CCL20作用可有效缓解关节炎症,且与雷公藤效果相当,CCL20单克隆抗体在临床治疗类风湿关节炎方面具有潜在价值.

Comparative study of CCL20 monoclonal antibody and tripterygium wilfordii in murine collagen-induced arthritis

Objective To investigate the expression of chemotactic factor CCL20 in murine collagen-induced arthritis(CIA) murines and the therapeutic effect of anti-CCL20 therapy on CIA,and to explore its potential value in the treatment of rheumatoid arthritis(RA).Methods ①The model of CIA was established,forty DBA/1 murines were randomly divided into four groups:healthy control group,CIA model group,CCL20 monoclonal antibody group,tripterygium wilfordii group;②Joint swelling degree of murines on different time points was observed;③The pathological changes were evaluated,and the serum tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) level were also measured;④The pathological changes in four groups were analyzed by the statistical SPSS 17.0.Results ①Comparing to that of control group,CCL20,TNF-α and IL-1β serum levels in CIA model group,tripterygium wilfordii group,CCL20 monoclonal antibody group increased significantly,CCL20(29.45±4.92) ng/L,(18.32±4.80) ng/L,(14.13±3.82) ng/L vs(2.83±1.37) ng/L;TNF-α(63.1±2.82) ng/L,(43.15±2.31) ng/L,(42.91±2.02) ng/L vs(26.78±3.50) ng/L;IL-1β(83.72±4.04) ng/L,(53.78±5.89) ng/L,(56.77±4.98) ng/L vs(16.54±2.45) ng/L,CCL20,TNF-α and IL-1β serum levels in tripterygium wilfordii group and CCL20 monoclonal antibody group were both significantly lower than those in CIA model group.②In HE staining observation,CIA model group showed more changes than control group in synovial membrane thickening,confused arrangement,obvious infiltration of inflammatory cell in synovial membrane,pannus formation,tripterygium wilfordii group,CCL20 monoclonal antibody group lessened significantly than CIA model group.Conclusion Expression of CCL20 is up-regulated in CIA murine;blocking the expressions by CCL20 monoclonal antibody can effectively relieve the joint inflammation,and its effect of treatment is similar to tripterygium wilfordii.CCL20 monoclonal antibody has potential value in treatment of RA.