糖皮质激素治疗SLE的效果与外周血单个核细胞P-gp表达水平的相关性

Correlation of P-glycoprotein Expression on Peripheral Blood Mononuclear Cells with Effect of Glucocorticoid on Systemic Lupus Erythematosus

目的:探讨外周血单个核细胞(PBMCs)膜表面P-糖蛋白(P-gp)的表达以评估糖皮质激素治疗系统性红斑狼疮(SLE)的敏感性。方法:采用梯度密度离心法分离24例SLE患者和15名健康人的PBMCs,半定量RT-PCR法检测MDR-1基因mRNA的表达,流式细胞仪检测P-gp的表达。结果:糖皮质激素敏感组的SLE患者与糖皮质激素抵抗组的SLE患者的PMBCs上MDR-1基因与P-gp的表达水平均高于健康对照组(P<0.05,P<0.01),糖皮质激素抵抗组的患者PMBCs上MDR-1基因与P-gp的表达水平明显高于糖皮质激素敏感组的SLE患者(P<0.05)。结论:PBMCs膜表面P-gp高表达的SLE患者对糖皮质激素治疗的反应性差,P-gp的表达水平可做为衡量SLE患者糖皮质激素治疗效果的敏感标志。

Objective： To determine whether the expression level of P-glycoprotein （P-gp） on peripheral blood mononuclear cells （PBMCs） to evaluate the glucocortieoid responsiveness in the patients with systemic lupus erythematosus （SLE）. Methods： Fifteen normal volunteers and 24 patients with SLE were involved in this study, and nine of them were classified as poor responders and fif- teen as good responders to the glueocorticoid therapy. PBMCs were isolated by density gradient centrifugation using lymphocyte separation medium. The expressions of P-gp and MDR-1 gene were measured by flow cytometry or semi-quantitative RT-PCR technique respectively. Results： The expression of P-gp and MDR-1 gene in the patients with good response and poor response to glucocorticoid therapy were significantly increased than in normal volunteers respectively （P（ 0.05 or P（0.01）. The patients with poor response to glucocorticoid therapy exhibited higher levels of P-gp and MDR-1 gene than the good responders did （P（0.05）. Conclusion： P-gp ex- pression seems to be involved in the poor response to glueoeorticoid treatment in active SLE patients. It has great value to predict glueocorticoid responsiveness by measuring P-gp levels on lymphoeytes and to make a patient-tailored regimen to control the disease activity of SLE patients with less side-effect.