CAJ | 학술논문

目的探讨1,25-二羟维生素D3[1,25(OH)2D3]对初诊RA患者NF-κB受体活化因子配体/骨保护素(RANKL/OPG)通路及相关细胞因子的作用及其治疗RA潜在的机制.方法选取初诊RA患者18例,符合1987年ACR分类标准.健康对照18名,来自我院医务人员的健康志愿者,其性别和年龄均与RA患者相匹配.分离RA患者PBMCs,加抗CD3和CD28刺激,1,25(OH)2D3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、IFN-γ,ELISA检测细胞RANKL、骨保护素水平.采用正态性检验和方差齐性检验,满足正态性和方差齐性条件,采用完全随机两样本t检验和单因素方差分析进行统计学处理.结果 RA组血清RANKL[(100±22) pmol/L]、TNF-α[(5.91±2.53) pg/ml]、IL-17[(43±6)pg/ml]、IL-6 [(16.6±12.0) pg/ml]水平显著高于对照组,2组比较差异有统计学意义(P＜0.05);RA组RANKL、TNF-α、IL-17、IL-6水平经不同浓度1,25(OH)2D3处理的效果差异有统计学意义(P＜0.05),各组组间经多重比较差异无统计学意义;1,25(OH)2D3降低RA组IL-17/IL-4、TNF-α/IL-4、IFN-γ/IL-4的比值.结论 1,25(OH)2D3作为一种免疫调节剂,对于RA软骨/骨损伤可能具有治疗作用.
목적 탐토1,25-이간유생소D3[1,25(OH)2D3]대초진RA환자NF-κB수체활화인자배체/골보호소(RANKL/OPG)통로급상관세포인자적작용급기치료RA잠재적궤제.방법 선취초진RA환자18례,부합1987년ACR분류표준.건강대조18명,래자아원의무인원적건강지원자,기성별화년령균여RA환자상필배.분리RA환자PBMCs,가항CD3화CD28자격,1,25(OH)2D3화(혹)갑안접령공배양,류식세포의미구포획심편기술(CBA)검측IL-4、IL-6、TNF-α、IL-17A、IFN-γ,ELISA검측세포RANKL、골보호소수평.채용정태성검험화방차제성검험,만족정태성화방차제성조건,채용완전수궤량양본t검험화단인소방차분석진행통계학처리.결과 RA조혈청RANKL[(100±22) pmol/L]、TNF-α[(5.91±2.53) pg/ml]、IL-17[(43±6)pg/ml]、IL-6 [(16.6±12.0) pg/ml]수평현저고우대조조,2조비교차이유통계학의의(P＜0.05);RA조RANKL、TNF-α、IL-17、IL-6수평경불동농도1,25(OH)2D3처리적효과차이유통계학의의(P＜0.05),각조조간경다중비교차이무통계학의의;1,25(OH)2D3강저RA조IL-17/IL-4、TNF-α/IL-4、IFN-γ/IL-4적비치.결론 1,25(OH)2D3작위일충면역조절제,대우RA연골/골손상가능구유치료작용.
Objective To investigate whether the modulation of Th1/Th17 and Th2 cytokine balance and the inhibition of receptor activator of nuclear factor-κB ligand (RANKL) expression of 1,25(OH)2-Vitamin -D3 in the treatment of rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected.The cells were stimulated with monoclonal antibodies to CD3 and CD28 in the absence or presence of 1,25(OH)2-Vitamin-D3 and MTX.After co-incubation,the levels of Th1 cytokines IFN-γ,Th17 cytokines IL-17,IL-6,TNF-α,and Th2 cytokines IL-4 were analyzed by cytometric 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-way ANOVA were used for statistics analysis.Results The levels of RANKL [(100±22) pmol/L],TNF-α [(5.91±2.53) pg/ml],IL-17 [(43±6) pg/ml]and IL-6 [(16.6±12.0) pg/ml] expression in the serum of RA patients were significantly higher than those of the control group (P＜0.05).1,25 (OH)2-Vitamin-D3 inhibited the RANKL,TNF-α,IL-17 and IL-6 expression in the RA group.Moreover,1,25(OH)2-Vitamin-D3 decreased the ratios of IFN-γ/IL-4,TNF-α/IL-4 and IL-17/IL-4 in RA group.Conclusion Our data suggest that 1,25-dihydroxyvitamin D3 may play an important role in the maintenance of T cell cytokines and RANKL/OPG pathway homeostasis,and correction of vitamin D deficiency may be useful in the treatment of T cell mediated autoimmune disorders and RA.