1，25-二羟维生素D3对初诊类风湿关节炎患者核因子κB受体活化因子配体／骨保护素通路及相关细胞因子的影响

1,25 （OH）2Vitamin-D3 attenuates the expression of receptor activator of nuclear factor.KB ligand/osteopr- otegerin and related cytokines expression in the peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis

【摘要】目的探讨1，25-二羟维生素D3[1，25（OH），D，]对初诊RA患者NF—KB受体活化因子配体／骨保护素（RANKL／OPG）通路及相关绑胞因子的作埔及其渝疗RA潜在的机制？方法选取初诊RA患者l8例，符合1987年ACR分类标准。健康对照18辊，来自我院医务人员的健康志愿者，其性圳和年龄均j-jRA患者相匹配、允离RA患者PBMCs，加抗CD3和CI）28刺激，l，25（OH），D，和（或）甲氨蝶呤共培养，流式细胞仪微球捕获芯片技术（CBA）检测IL-4、IL-6、TNF-α、IL-17A、[FN-γ，ELISA检测细胞RANKL骨保护素水平。采用正态性柃验和方差齐性检验，满足正态性和方差齐性条件，采用完全随机两样书，检验和单因素方差分析进行统计学处理。结果RA组lJ0【清RANKL[（100＋22）pmool／L、TNF—di（5．91±2．53）1）pg/ml] IL-17[（43±6）vg／mt]、IL-61（16．6±12．0）pg／m1]水平显著高于对照组，2组比较差异打统计学意义（P〈O．05）；RA组RANKL、TNF-d、IL-17、IL-6水平经不同浓度1，25（01f），D，处理的效果差异存统计学意义（P〈O．05），各组组问经多重比较差异无统计学意义；1，25（OH），I）、降低RA组IL-17／IL-4、TNF-α、IL-17A、[FN-γ 的比值.结论1，25（OH）2D3作为一种免疫渊节剂，对于RA软骨/骨损伤可能具有治疗作用．

Objective To investigate whether the modulation of Thl[l＇h17 and Tb2 cytokine balance and the inhibition of receptor aelivator of nuclear factmKB ligand （RANKL） expression of 1,25（OH ）e-Vitamin -D3 in the treatment of rheumatoid arthritis （RA）. Methods Peripheral blood mononuclear cells （PBMCs） tom healthy donors and RA patients were collected. The c＇ells were stimulated with monoclonal anlibodies to CD3 and CD2g in the absence or presence of 1,25（OH ）e-Vitamin-I）3 and MTX. After co-incubation, the levels of Thl cytokines IFN-y, Thl7 cytokines IL-17, IL-6, TNF-ot, aml Th2 cytokines IL-4 were analyzed by eytometrie bead array and the levels of RANKL and osteoprotegerin （OPG） were analyzed by enzyme-linked immun-osorbent assay. The independent samples t test and one-,a＇W ANOVA were used for statisties analysis. Results The levels of RANKL I（10022） pmol/L], TNF-o [（5.91＋2.53） pg/ml], IL-17 [（436） pg/ml] and I[-6 （16.6＋-12.0） pg/mll expression in /he serum of t{A patients were significantly higher than those of the control group （P〈0.05）. 1,25 （OH）2-Vitamin-D： inhibited the RANKL, TNF-ct, IL-17 and IL-6 expression in the IIA group. Moreover, 1,25 （OH）e-Vitamin-D decreased the ratios of IFN-//IL-4, TNF-cd IL-4 and 11,-17/IL-4 in RA group. Conclusion Our data suggest that 1,25-dihydmxyvitamin D3 may play an important role in the maintenance of T cell cytokines and RANK[JOPG pathway homeostasis, and correction ofvitamin D deficiency may be useful in the treatment of T cell mediated autoimmune disorders and RA.