类风湿关节炎患者外周血淋巴细胞P-糖蛋白的表达水平及逆转耐药作用的研究  

Study of the expression of peripheral blood lymphocyte P-glycoprotein in rheumatoid arthritis patients and reversing P-glycoprotein-induced drug resistance

作　　者：赵向聪[1] 王彩虹[1] 罗静[1] 李雪飞[1] 刘晓剑[1] 李小峰[1] 

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001

出　　处：《中华风湿病学杂志》2013年第10期672-676,共5页Chinese Journal of Rheumatology

基　　金：山西省科技攻关项目（20110313013-1）;山西省卫生厅科研课题计划（201201072）

摘　　要：目的检测耐药分子P-糖蛋白（P-dycoprotein）在类风湿关节炎（RA）患者外周血淋巴细胞的表达水平及相关影响因素，探讨周期联合甲氨蝶呤或来氟米特与环磷酰胺对P-糖蛋白介导耐药性的逆转作用。方法本研究为横断面研究，纳入RA患者42例，其中初发组15例，治疗组27例，根据治疗前后类风湿关节炎疾病活动性评分（DAS28）的变化，治疗组分为治疗缓解组12例和难治组15例。按治疗方案，分为单用药组（甲氨蝶呤或来氟米特）、甲氨蝶呤＋来氟米特联合组，甲氨蝶呤或来氟米特＋环磷酰胺联合组。用流式细胞术测定外周血淋巴细胞P-糖蛋白的表达水平。采用SPSS13．0进行统计分析，方法采用两独立样本t检验、单因素方差分析、Bonferroni法和LSD法、计数资料比较采用χ2检验，Pearson相关性分析。结果①健康对照组、初发组、缓解组、难治组相对荧光强度（RFI）平均值分别为2．0±0．7、2．9±1．0、3．5±1．4、5．0±2．0，4组间总体比较差异有统计学意义（F=7．955，P〈0．01）。两两比较：健康对照组与初发组差异无统计学意义（P=0．137），缓解组与难治组比较差异有统计学意义（P=0．013）。②RA患者P．糖蛋白与性别、发病年龄、病程、类风湿因子（RF）滴度均无相关性，与红细胞沉降率（ESR）及DAS28呈正相关（r=0．447，P=0．002；r=0．398，P=0．012）；③单用药组（甲氨蝶呤或来氟米特）、甲氨蝶呤±来氟米特联合组，甲氨蝶呤或来氟米特＋环磷酰胺联合组P—gP表达水平的RFI值分别为5．1±2．2、6．0±1．2、3．4±1．1，甲氨蝶呤或来氟米特＋环磷酰胺联合组低于单用药组（P〈0．05），甲氨蝶呤＋来氟米特联合组表达水平高于单用药组，但差异无统计学意义。结论RA患者外周血淋巴细胞P．糖蛋白的表达水平和疾病活动平行，改变病情抗风湿药（DMARDs）�Objective To study the expression of peripheral blood lymphocyte P-glycoprotein （P-gp） and related impact factors in rheumatoid arthritis （RA） patients, and explore whether the periodic combination of methotrexate （MTX） or leflunomide （LEF） with cyclophosphamide （CTX） could reverse P-gpinduced drug resistance. Methods This study was a cross-sectional study. Forty-two RA patients were enrolled （ 15 cases in the primary untreatment group, while 27 cases in the treatment group）. In the treatment group, patients were divided into the improvement group （12 patients） and the refractory group （15 patients） respectively according to their disease activity scores （DAS 28）. According to the medication used, 42 patients were divided into 3 groups：the monotherapy group （MTX or LEF）, the MTX＋LEF combination treatment group and MTX or LEF＋CTX treatment group. The expression of peripheral blood lymphocyte P-gp in each group was detected by flow cytometry. T test, ANOVA, LSD test, Bonferroni test, χ2 test and Pearson correlation analysis were used for statistical analysis with software 13.0. Results ①） Mean relative fluorescence intensity （RFI） of P-gp was 2.0±0.7, 2.9±1.0, 3.5±1.4, 5.0±2.0 respectively in healthy control group, the primary untreatment group, the improvement group and the refractory group, the difference was signifi- cant （F=7.955, P〈0.01）. In multiple comparisons, the fluorescence intensity was higher in the primary untrea-tment group as compared to the healthy group, but the difference was not statistically significant（P=0.137）; however, it was significantly higher in the refractory group as compared to the improvement group （P=0.013）. ② There was no correlation between the expression of P-gp in RA patients and sex, age of onset, disease duration or positive rate of RF. But the expression of P-gp was significantly correlated with ESR and DAS28 （r=0.447, P=0.002; r=0.398, P=0.012）. ③ RFI of the P-gp group was 5.1±2.2, 6.0±1.2, 3.

关 键 词：关节炎 类风湿 P糖蛋白 甲氨蝶呤 环磷酰胺 抗药性 

分 类 号：R593.22[医药卫生—内科学]