糖皮质激素受体α在系统性红斑狼疮发病机制中的作用研究

Study of the role of glucocorticoid receptor α in the pathogenesis of systemic lupus erythematosus

目的探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)糖皮质激素受体!(GR!)mRNA表达及其与免疫指标[抗核抗体(ANA)、抗dsDNA抗体]的变化、疾病活动性的关系,分析GR!在SLE发病机制中的作用。方法采用反转录聚合酶链反应(RT-PCR)检测活动期和缓解期SLE患者和正常人PBMCs中GR!mRNA的表达,并将其与ANA、抗dsDNA抗体及疾病活动性作相关分析。结果SLE患者PBMCs中GR!mRNA表达较正常人明显减少(P<0.05),但活动期患者表达高于缓解期患者(P<0.05),且与抗dsDNA抗体及疾病活动性呈负相关。结论SLE患者外周血PBMCs存在GR!的表达缺陷,从而引起对自身反应性T、B淋巴细胞的活化缺乏抑制效应,导致自身免疫耐受丧失,产生炎症性细胞因子和自身抗体。GR!在SLE的发病机制中可能发挥重要作用。

Objeαive To investigate the expression of GRα mRNA in the peripheral blood mononuclear cells （PBMCs） of SLE patients and analyze the relationship between GRα and immune parameters, SLEDAI score, in order to reveal the role of GRα in the pathogenesis of SLE. Methods Applying reverse transcription-polymerase chain reaαion （RT-PCR） technique to semiquantitatively analyze GRα mRNA expression in SLE patients and healthy volunteer individuals. The relationship between GRα and ANA, anti-dsDNA antibodies, SLEDAI score was analyzed. Results The expression of GRα mRNA in SLE was significantly lower than that of control group （P〈0.05）. But the expression of GRα in aαive patients was obviously higher than that of inaαive patients （P〈0.05）, and associated negatively with anti--ds-DNA antibodies and SLEDAI score. Conclusion The defeαive expression of GRα mRNA exists in the PBMCs of SLE patients. This results in lacking inhibition to autoreaαive T,B cells from aαivation. As a result, losing the autotolerance leads to produce inflammatory cytokines and autoantibndies, and this plays an important role in the pathogenesis of SLE.