PAMPs对抗体诱导类风关样小鼠模型的影响  

Effects of PAMPs on the mouse arthritis model induced by antibodies

作　　者：刘万成[1] 杨雪姣[1] 祝元锋[1] 鲁永玲[1] 范仕郡[1] 李彦[1] 

机构地区：[1]第三军医大学西南医学院综合研究中心,重庆400038

出　　处：《免疫学杂志》2016年第9期804-808,共5页Immunological Journal

基　　金：重庆市前沿与基础研究重点项目(cstc2013jj B10024)

摘　　要：目的探讨病原相关模式分子（PAMPs）对抗体诱导的关节炎（CAIA）样小鼠模型建立的影响。方法 7~8周龄Balb/c雌鼠,第0天使用抗体混合物诱导,第3天使用LPS（TLR4激动剂）或Cp G ODN 1826（TLR9激动剂）激发,每天定时观察四肢关节发病情况并进行关节评分;小鼠腹腔注射O111：B4和O55：B5,绘制生存曲线进行毒性分析;ELISA检测PAMPs刺激小鼠巨噬细胞后IL-6、TNF-α的分泌水平;鲎实验定量检测相同浓度下O111：B4和O55：B5的有效活性。结果 PAMPs成功激发CAIA模型炎症,其中O55：B5低死亡率、高成模率;O111：B4的毒性强于O55：B5;O55：B5的炎症因子分泌量显著高于O111：B4和Cp G ODN 1826（P〈0.01）;O111：B4的有效活性显著高于O55：B5（P〈0.01）。结论低毒高致炎性的O55：B5激发模型效果最佳,说明PAMPs能够影响建模效果,而低毒高致炎性PAMPs适合该模型的激发。Rheumatoid arthritis is a chronic inflammatory disorder, and the mechanism remains unknown. Thelatest collagen antibody induced arthritis（CAIA） model is an antibody mediated model of the effector phase ofarthritis, but joint inflammation is enhanced by an additional immunostimulatory agent for experimental needs,because antibody injection alone induces mild arthritis. Pathogen-associated molecular patterns（PAMPs） canactivate the innate immune system through cytokine production, and enhance joint inflammation asimmunostimulatory agent, but what kind of PAMPS is more suitable for the model is not clear. Here, we aimed toinvestigate the effect of PAMPs on CAIA. Balb/c female mouse of 7-8 weeks old were used as the experimentalanimals. The cocktail of antibody was injected on day 0, LPS（TLR4 agonist） or Cp G-ODN 1826（TLR9 agonists） onday 3. Then the situation of the four limbs joints was observed at regular interval in every day and the arthritic indexwas scored. Intraperitoneal administration of O111：B4 and O55：B5 was carried out, and survival curve of mice wasdrawn and the toxicity was analyzed. The levels of IL-6 and TNF-α released by macrophage after PAMPs treatmentwere detected by ELISA. The effective activity of O111：B4 and O55：B5 at the same concentration was tested bylimulus test. Data showed that PAMPs induced CAIA successfully, and O55：B5 showed low mortality and high rateof modeling. O111：B4 had higher toxic than O55：B5. The production of inflammatory factor induced by O55：B5 washigher than that induced by O111：B4 and Cp G ODN 1826（P〈0.01）. The effective activity of O111：B4 was higherthan O55：B5（P〈0.01）. In conclusion, with low lethality and high proinflammatory effects, O55：B5 should be the bestone for stimulating CAIA, suggesting that PAMPs do influence the modeling of CAIA, and the PAMPs of lowlethality and high proinflammatory effects is suitable for the stimulation of the arthritis model.

关 键 词：类风湿性关节炎 抗体诱导的RA模型 病原相关模式分子 TOLL样受体 

分 类 号：R593.22[医药卫生—内科学]