核因子-κB寡脱氧核苷酸策略对胶原诱导关节炎大鼠细胞因子调节研究

Research of nuclear factor-κB oligodeoxynucleotide targeting strategy on cytokine regulation in collagen induced arthritic rats model

目的:探讨核因子-κB(NF-KB)寡脱氧核苷酸(ODN)局部应用对Ⅱ型胶原诱导关节炎(CIA)大鼠的治疗作用及机制。方法:建立Ⅱ型CIA大鼠模型,用NF-κB圈套ODN注射到大鼠右后踝关节腔内,并设空白对照组、CIA模型组和实验组。42 d后观察各组关节炎指数、病理指标,采用酶联免疫吸附试验法检测各组大鼠血清和关节液中白细胞介素(IL)-17、IL-12和转化生长因子-β(TGF-β)的水平。结果:与空白对照组比较,CIA模型组大鼠血清和关节液中IL-17和IL-12水平均明显升高,而TGF-β水平显著降低(P<0.01),而实验组经NF-κB圈套ODN注射后,与CIA模型组比较,血清和关节液中IL-17和IL-12水平均明显降低,而TGF-β水平显著升高(P<0.01)。结论:NF-κB圈套ODN明显抑制CIA大鼠外周血和关节液中IL-17、IL-12的产生,促进TGF-β水平的增加,对CIA有较好的治疗作用。

Objective： To investigate the therapeutic effect of nuclear factor-κB（ NF-κB） oligodeoxynucleotide（ ODN） Decoy topical application on typeⅡ collagen induced arthritis（ CIA） rats and analyze its mechanism. Methods： Type Ⅱ CIA rats was established,NF-κB ODN Decoy was injected into the posterior ankle cavity of rats. The rats were divided into control group,CIA model group and experimental group. Forty-two days after the initial immunization,the arthritis scores were determined,the ankle pathology examination were performed,the interleukin（ IL）-17,IL-12 and transforming growth factor（ TGF）-β levels in serum and joint fluid were determined using by enzyme linked immunosorbent assay method. Results： Compared with control rats,IL-17,IL-12 levels in serum and joint fluid in model CIA rats were increased significantly,and TGF-β level was decreased（ P〈0. 01）. After the CIA rats were received with NF-κB ODN Decoy,compared with CIA rats,IL-17,IL-12 levels in serum and joint fluid were decreased significantly,and TGF-β level was increased significantly（ P〈0. 01）. Conclusions： NF-κB decoy had significantly inhibited the production of IL- 17,IL – 12 in serum and joint fluid and promoted the increase of TGF-β,and it had a good curative effect on treatment of rheumatoid arthritis.