内源性库欣综合征患者外周血糖皮质激素受体敏感性的检测

The Functional Analysis of Glucocorticoid Receptor in Peripheral Blood of Endogenous Cushing's Syndrome Patients

目的检测内源性库欣综合征患者体内糖皮质激素受体(GR)的数量与结合力的改变,为库欣综合征患者术后糖皮质激素合理替代治疗剂量提供参考。方法按入院顺序依次纳入在四川大学华西医院内分泌代谢科住院并诊断为内源性库欣综合征的患者,并选择年龄及性别与患者匹配的健康志愿者作为对照组。采用流式细胞术检测两组受试者单个核细胞(PBMC)GR的数量和结合力,比较两组受试者差异,并分析库欣综合征患者血尿皮质醇水平与其GR数量及结合力的相关性。结果共纳入库欣综合征患者17例和健康志愿者17例。库欣综合征患者GR数量和结合力分别为11.9±3.1、6.6±2.6;正常对照组GR数量和结合力分别为20.6±3.3、9.9±3.2。库欣综合征患者GR数量和结合力低于正常组(P<0.05);库欣综合征患者血、尿皮质醇水平与其GR数量或结合力无相关关系。结论库欣综合征患者GR敏感性明显降低,建议手术切除肿瘤后患者采用生理剂量1.6倍的糖皮质激素替代治疗,以克服患者的糖皮质激素抵抗,维持糖皮质激素的生理功能。

Objective To evaluate the expression level and binding affinity glucocorticoid receptor(GR)in endogenous Cushing’s syndrome patients.Methods The patients of endogenous Cushing’s syndrome were enrolled in the department of endocrinology in West China Hospital of Sichuan University,and age-and sex-matched healthy volunteers were studied as control group.The expression level and binding affinity of GR in peripheral blood mononuclear cells(PBMCs)were examined by flow cytometry.The differences between the two groups were compared,and the correlations of GR level and affinity to serum cortisol concentration or 24 hurine free cortisol were also analyzed.Results There were 17Cushing’s syndrome patients and 17 healthy volunteers.The expression level and binding affinity of GR in Cushing’s syndrome patients were 11.9±3.1and 6.6±2.6,while the values of normal controls were 20.6±3.3and 9.9±3.2.A significant decrease in GR expression and binding affinity in the patients with Cushing’s syndrome was found.No correlation was observed between plasma cortisol concentration or24 hurinary free cortisol and GR expression or binding affinity in Cushing’s syndrome patients.Conclusion The expression level and binding affinity of GR are obviously decreased in Cushing’s syndrome patients,which suggests1.6times of physiological dose of glucocorticoid for the patients with hypocortisolism after surgery,in order to overcome glucocorticoid resistance and maintain physiological function of glucocorticoid.