In order to investigate efficacy of FGF21 combine dexamethasone (Dex) on rheumatoid arthritis (RA) meanwhile reduce side effects of dexamethasone. We used combination therapy (Dex 15 mg/kg + FGF21 0.25 mg/kg, Dex 15 mg/kg + FGF21 0.5 mg/kg or Dex 15 mg/kg + FGF21 1 mg/kg) and monotherapy (Dex 15 mg/kg or FGF21 1 mg/kg) to treat CIA mice induced by chicken type II collagen, respectively. The effects of treatment were determined by arthritis severity score, histological damage, and cytokine production. The levels of oxidative stress parameters, liver functions, and other blood biochemical indexes were detected to determine FGF21鈥檚 efficiency to side effects of dexamethasone. Oil red O was performed to detect the effects of FGF21 and dexamethasone on fat accumulation in HepG2 cells. The mechanism of FGF21 improves the side effects of dexamethasone which was analyzed by Western blotting. This combination proved to be therapeutically more effective than dexamethasone or FGF21 used singly. FGF21 regulates oxidative stress and lipid metabolism by upregulating dexamethasone-inhibited SIRT-1 and then activating downstream Nrf-2/HO-1and PGC-1. FGF21 and dexamethasone are highly effective in the treatment of arthritis; meanwhile, FGF21 may overcome the limited therapeutic response and Cushing鈥檚 syndrome associated with dexamethasone.

为了研究FGF21联合地塞米松（Dex）对类风湿性关节炎（RA）的疗效，同时降低地塞米松的副作用。我们使用联合疗法（Dex 15 mg/kg + FGF21 0.25 mg/kg、Dex 15 mg/kg + FGF21 0.5 mg/kg 或 Dex 15 mg/kg + FGF21 1 mg/kg）和单一疗法（Dex 15 mg/kg 或FGF21 1 mg/kg) 分别治疗鸡 II 型胶原诱导的 CIA 小鼠。治疗效果由关节炎严重程度评分、组织学损伤和细胞因子产生决定。检测氧化应激参数、肝功能及其他血液生化指标水平，确定FGF21鈥檚对地塞米松副作用的有效率。油红O检测FGF21和地塞米松对HepG2细胞脂肪积累的影响。通过Western印迹分析FGF21的机制改善地塞米松的副作用。事实证明，这种组合在治疗上比单独使用地塞米松或 FGF21 更有效。FGF21通过上调地塞米松抑制的SIRT-1然后激活下游Nrf-2/HO-1和PGC-1来调节氧化应激和脂质代谢。FGF21和地塞米松治疗关节炎非常有效；同时，FGF21可能克服与地塞米松相关的有限治疗反应和库欣鈥檚综合征。FGF21和地塞米松治疗关节炎非常有效；同时，FGF21可能克服与地塞米松相关的有限治疗反应和库欣鈥檚综合征。FGF21和地塞米松治疗关节炎非常有效；同时，FGF21可能克服与地塞米松相关的有限治疗反应和库欣鈥檚综合征。