多药耐药性基因1/P糖蛋白(mdr1/P-gp)高表达与类风湿性关节炎患者甲氨蝶呤耐药有关

Over-expression of mdr1/P-gp is associated with methotrexate resistance in patients with rheumatoid arthritis

目的研究类风湿性关节炎(RA)患者甲氨蝶呤(MTX)耐药性与外周血单个核细胞(PBMC)多药耐药性基因1/P糖蛋白(mdr1/P-gp)的表达的相关性。方法根据符合纳入标准的RA患者依据服用MTX后28个关节疾病活动度评分(DAS28)的情况,将RA患者分为MTX敏感组及耐药组,健康人群为正常对照组。采用实时定量PCR检测mdr1 mRNA的表达,流式细胞术检测PBMC的P-gp的水平及功能,比较mdr1/P-gp在各组中的表达情况。结果与正常对照组相比,MTX敏感组及MTX耐药组P-gp表达及功能增强;与MTX敏感组相比,MTX耐药组mdr1 mRNA水平增加,且P-gp表达及功能增强。结论 RA患者mdr1/P-gp高表达与MTX耐药相关。

Objective To investigate the relationship between the gene expression of multidrug resisitance 1（ mdr1）/P-glycoprotein（ P-gp） in peripheral blood mononuclear cells（ PBMCs） and methotrexate（ MTX） resistance in patients with rheumatoid arthritis（ RA）. Methods According to the grades of disease activity score 28（ DAS28） after taking MTX,RA patients were divided into sensitive group and resistant group. In addition,the healthy volunteers were enrolled as a control group. Real-time PCR was adopted to detect the expression of mdrl mRNA,and flow cytometry was used to detect the level and function of P-gp in PBMCs. Using the information obtained from these detections,we compared the expression of mdr1/P-gp between the three groups. Results Compared with the healthy group,the expression of P-gp was higher in the sensitive group and resistant group. Compared with the sensitive group,both mdr1 mRNA and P-gp expressions increased in the resistant group. Conclusion The over-expression of mdr1/P-gp in RA patients is related to the MTX resistance.