CAJ | 학술논문

目的：探讨系统性红斑狼疮（ SLE）及类风湿关节炎（ RA）外周血单个核细胞（ PBMCs）中糖皮质激素受体（GR）4种亚型GRα、GRβ、GRγ、GR-P及血浆中白细胞介素（IL）-6、巨噬细胞游走抑制因子（ MIF）、干扰素（ IFN）-γ和IL-10表达及差异，同时分析与疾病活动相关性。方法选择初发SLE患者55例、RA患者49例和健康对照38例，采用实时定量逆转录－聚合酶链反应（ RT-PCR）法检测SLE、RA患者和对照PBMCs中GRα、GRβ、GRγ、GR-P表达，GR总和表达为4种GR亚型表达总和，酶联免疫吸附试验法检测血浆中IL-6、MIF、IFN-γ和IL-10表达。结果 SLE、RA患者及对照4种GR亚型表达占GR总和百分比呈以下趋势：GRα＞GR-P＞GRγ＞GRβ。与对照相比， SLE和RA患者GRα表达所占百分比显著降低（P＜0．05），GR-P显著高于对照（P＜0．05）。 RA患者GR-P表达显著高于SLE组（P＜0．05）。 SLE患者和RA患者GRα表达与SLEDAI评分呈显著负相关（P＜0．05），RA患者GRα表达与DAS28评分呈显著负相关（P＜0．05）；从表达来看，高活动组GRα表达显著低于低活动组（P＜0．05）。与对照相比，SLE、RA患者IL-6、IFN-γ和MIF表达均显著增高（P＜0．05）。 SLE高活动组IL-6显著高于低活动组（P＜0．05）。 RA患者高活动组IFN-γ表达显著高于低活动组（P＜0．05）。 SLE组高活动患者IL-6与GRα表达呈显著负相关（ P＜0．05）；RA组高活动组IFN-γ与GRα表达呈显著负相关（P＜0．05）。结论 SLE、RA患者GR亚型表达特点与对照不同，且两种疾病间亦存在差异，提示两种疾病发病时内环境变化可导致GR各亚型比例的变化。 GRα为GR表达最主要亚型，与疾病活动呈负相关，炎性细胞因子过量分泌对GRα可能有抑制作用，本研究结果对临床判断疾病活动度、指导临床用药有重要意义。
목적：탐토계통성홍반랑창（ SLE）급류풍습관절염（ RA）외주혈단개핵세포（ PBMCs）중당피질격소수체（GR）4충아형GRα、GRβ、GRγ、GR-P급혈장중백세포개소（IL）-6、거서세포유주억제인자（ MIF）、간우소（ IFN）-γ화IL-10표체급차이，동시분석여질병활동상관성。방법선택초발SLE환자55례、RA환자49례화건강대조38례，채용실시정량역전록－취합매련반응（ RT-PCR）법검측SLE、RA환자화대조PBMCs중GRα、GRβ、GRγ、GR-P표체，GR총화표체위4충GR아형표체총화，매련면역흡부시험법검측혈장중IL-6、MIF、IFN-γ화IL-10표체。결과 SLE、RA환자급대조4충GR아형표체점GR총화백분비정이하추세：GRα＞GR-P＞GRγ＞GRβ。여대조상비， SLE화RA환자GRα표체소점백분비현저강저（P＜0．05），GR-P현저고우대조（P＜0．05）。 RA환자GR-P표체현저고우SLE조（P＜0．05）。 SLE환자화RA환자GRα표체여SLEDAI평분정현저부상관（P＜0．05），RA환자GRα표체여DAS28평분정현저부상관（P＜0．05）；종표체래간，고활동조GRα표체현저저우저활동조（P＜0．05）。여대조상비，SLE、RA환자IL-6、IFN-γ화MIF표체균현저증고（P＜0．05）。 SLE고활동조IL-6현저고우저활동조（P＜0．05）。 RA환자고활동조IFN-γ표체현저고우저활동조（P＜0．05）。 SLE조고활동환자IL-6여GRα표체정현저부상관（ P＜0．05）；RA조고활동조IFN-γ여GRα표체정현저부상관（P＜0．05）。결론 SLE、RA환자GR아형표체특점여대조불동，차량충질병간역존재차이，제시량충질병발병시내배경변화가도치GR각아형비례적변화。 GRα위GR표체최주요아형，여질병활동정부상관，염성세포인자과량분비대GRα가능유억제작용，본연구결과대림상판단질병활동도、지도림상용약유중요의의。
Objective To analyze the differences with the expression of glucocorticoids receptor isoforms ( GRα, GRβ, GRγand GR-P ) and cytokines [ IL-6, macrophage migration inhibitory factor (MIF), IFN-γand IL-10] between patients with systemic lupus erythematosus (SLE) and rheumatoid ar-thritis ( RA) , and to further understand their correlations with disease activities.Methods Fifty-five pa-tients with SLE, forty-nine patients with RA and thirty-eight healthy subjects were recruited in this study. All patients were steroid-naive.The expression of GRα, GRβ, GRγ, and GR-P in peripheral blood mononu-clear cells at transcript levels were determined by real-time PCR.Enzyme-linked immunosorbent assay was used to detect the expression of IL-6, MIF, IFN-γand IL-10 in serum samples.Results The percentages of GRαin all subjects were the highest among four isoforms of GR, followed by GR-P, GRγand GRβ.Com-pared with healthy subjects, patients with SLE or RA showed significantly decreased expression of GRα( P<0.05), but increased expression of GR-P (P<0.05).The percentages of GR-P in patients with RA were higher than those in patients with SLE (P<0.05).The expression of GRαwas negatively correlated with SLE disease activity index (SLEDAI) and disease activity score 28 (DAS28).SLE or RA patients with high disease activity showed lower expression of GRαthan those with low disease activity.The levels of IL-6, IFN-γand MIF in patients with SLE or RA were significantly higher than those in healthy subjects ( P<0.05).A negative correlation was observed between the expression of IL-6 and GRαin patients with SLE (P<0.05).The expression of IFN-γwas negatively correlated with GRαin patients with RA (P<0.05). Conclusion There were significant differences with the expression of GR isoforms among patients with SLE, patients with RA and healthy subjects, indicating the change of internal environment in patients might be in-volved in GR alternative splicing.GRαwas the predominant isoform and was negatively correlated with dis-ease activities.Oversecretion of cytokines resulted in a decreased expression of GRα.This study would be useful for the diagnosis of the disease status and for monitoring clinical treatment.