激素抵抗型系统性红斑狼疮患者外周血单核细胞中糖皮质激素受体α的表达及其核质分布

Expression and nucleoplasm distribution of glucocorticoid receptor alpha of peripheral blood mononuclear cell in patients with glucocorticoid-resistant systemic lupus erythematosus

目的探讨激素抵抗型系统性红斑狼疮(SLE)患者外周血单核细胞(PBMC)中糖皮质激素受体α(GRα)表达的量及核质分布,推测SLE激素抵抗发生的可能机制。方法选取激素抵抗型SLE患者、激素敏感型SLE患者和健康对照各18例。SLE患者在完成治疗8周后,抽取所有对象外周血,分离单个核细胞,用Western Blot检测GRα表达量,用免疫组化技术检测GRα核质比。结果激素敏感组及激素抵抗组PBMC中GRα表达明显低于健康对照组(P<0.05);激素抵抗组核质比低于敏感组及健康对照组(P<0.05)。结论 GRα表达的下调及其核转运障碍可能在SLE患者糖皮质激素抵抗的发生中发挥关键作用。

Objective To investigate the expression and nucleoplasm distribution of glucocorticoid receptor alpha（GRα） of peripheral blood mononuclear cell（PBMC） in patients with glucocorticoid-resistant systemic lupus erythematosus（SLE）,aiming at conjecture the possible pathogenesis of glucocorticoid-resistant SLE.Methods Glucocorticoid-resistant SLE patients, glucocorticoid-sensitive SLE patients,and healthy controls,each of 18 cases,were selected.Eight weeks after the SLE patients had received the treatment,the peripheral blood of all subjects was extracted,and PBMC was isolated to determine the expression level of GRαby using Western Blot and GRαnucleocytoplasmic ratio by the immunohistochemistry technique.Results The glucocorticoid-resistant or glucocorticoid-sensitive SLE patients showed significantly lower expression level of GRαof PBMC compared with healthy controls（P 〈0.05）,and the nucleocytoplasmic ratio in glucocorticoid-resistant SLE patients was lower than that in glucocorticoid-sensitive SLE patients or healthy controls（P 〈0.05）. Conclusion The down-regulation of GRαexpression and nuclear transport barriers might play a key role in the activation of GC resistance among SLE patients.