Bmi-1抑制剂PTC-209减轻自身免疫关节炎模型小鼠炎症及骨侵蚀

Bmi-1 inhibitor PTC-209 alleviates inflammation and bone erosion in mice model of autoimmunearthritis

目的探索Bmi-1抑制剂PTC-209在自身免疫关节炎小鼠中的治疗作用。方法构建自身免疫关节炎模型小鼠,在3次免疫后开始连续腹腔注射Bmi-1抑制剂PTC-209(50 mg/kg)7 d。期间对关节炎小鼠进行体重和发病情况评分。利用组织病理学观察Bmi-1抑制剂对关节炎小鼠炎症及骨侵蚀的影响。结果与对照组相比,应用PTC-209的AIA小鼠关节炎评分降低,滑膜增生减少,关节区域肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)炎症因子表达降低。小鼠PTC-209小分子可以减少关节软骨区域的骨胶原流失并且增加软骨区域的厚度,除此之外还可以减少骨小梁区域中TRAP+破骨细胞的数量。结论PTC-209可以缓解AIA小鼠疾病进展,减少炎症及骨破坏。

Objective To investigate the effect of Bmi-1 inhibitor PTC-209 on autoimmune arthritis(AIA)in mice.Methods After 3 immunizations,intraperitoneal injection of Bmi-1 inhibitor PTC-209(50mg/kg)was performed for continuous 7 days to establish mice model of AIA.During this period,the arthritic mice were scored for their body weight and morbidity.Histopathology was used to determine the effect of Bmi-1 inhibitor on inflammation and bone erosion in arthritic mice.Results Compared with the control group,the arthritis scores decreased,synovial hyperplasia was reduced,and the expression levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)inflammatory factors in the joint area decreased in AIA mice treated by PTC-209.Small molecule inhibitor PTC-209 reduced the collagen lossin the articular cartilage area and increased the thickness of the cartilage area.In addition,it also reduced the number of TRAP+osteoclasts in the trabecular bone area.Conclusion PTC-209 may alleviate the disease progression in AIA mice,and thereby reduce inflammation and bone destruction.