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目的:探讨IL-1β对RA患者滑膜成纤维细胞(FLS)中乳腺癌耐药蛋白(BCRP/ABCG2)mRNA表达的影响,探索IL-1β对BCRP介导多药耐药性的调控作用。方法:获取RA 3例和OA 3例患者FLS,建立FLS体外培养体系,培养至Ⅴ代;①采用实时荧光定量PCR(RT-qPCR)检测RA与OA的FLS中BCRP mRNA的表达水平并比较;②评估RA病情活动度与BCRP mRNA的表达水平的相关性;③ RA-FLS分为4组,A组空白对照组,B组、C组、D组分别加入20、50、100 ng/ml的IL-1β,培养24、48、72 h,比较不同组间BCRP mRNA表达水平。定量资料采用n M(n P25,n P75)表示,两独立样本比较采用Mann-Whitney n U检验,组间比较采用Friedman检验。n 结果:① RA-FLS中BCRP mRNA表达水平高于OA组[0.68(0.26,1.16)与0.06(0.05,0.53);n Z=-2.136,n P=0.029]。② RA-FLS的BCRP mRNA的表达量与病程、ESR、CRP及DAS28呈正相关趋势,而与发病年龄呈负相关趋势,与性别无相关性。③相同浓度IL-1β刺激不同时间RA-FLS的BCRP mRNA的表达水平比较:IL-1β浓度为0时,48 h和72 h较24 h BCRP mRNA的表达水平均升高(n χ2=6.00,n P=0.034);IL-1β浓度为20 ng/ml(n χ2=8.00,n P=0.014)或100 ng/ml (n χ2=6.50,n P=0.040)时,72 h组BCRP mRNA的表达水平较24 h组明显升高。④不同浓度IL-1β刺激相同时间RA-FLS的BCRP mRNA的表达水平比较:72 h时,100 ng/ml组较0 ng/ml组BCRP mRNA表达升高(n χ2=12.00,n P=0.006)。n 结论:RA-FLS存在BCRP介导的耐药性,且可能与病情活动度有关。炎性细胞因子IL-1β参与调控RA-FLS的BCRP mRNA的表达,且存在时间和浓度依赖性。“,”Objective:To explore the effects of different concentrations or time points of interleukin (IL)-1β on the expression of breast cancer resistance protein (BCRP) mRNA in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients.Methods:Synovium tissue of RA (n n=3) and osteoarthritis (OA, n n=3) patients was obtained through osteoarticular surgery and were used to establish FLS culture system n in vitro. FLS cells in generation V were used the following purposes. ① Comparing the expression levels of BCRP mRNA in RA-FLS and OA-FLS by real time quantitative polymerase chain reaction (RT-qPCR). ② Analyzing the correlation between the activity of the disease and the expression level of BCRP mRNA. ③ FLS cells were divided into A, B, C, D four groups: Group A was the control group. Group B, C, D were cocultured with low (20 ng/ml), moderate (50 ng/ml), high (100 ng/ml) concentrations of IL-1β for 24 h, 48 h, and 72 h respectively. The expression levels of BCRP mRNA in different groups were compared.n Results:① The expression of BCRP mRNA in FLS of RA patients was significantly higher than that in the OA group [0.68(0.26, 1.16) n vs 0.06(0.05, 0.53); n Z=-2.136, n P=0.029]. ② The expression of BCRP mRNA in FLS of RA patients had a positive association with the course of disease, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score based on 28 joint counts (DAS28), and a negative association with the age of onset, but had no correlation with gender. ③ While the concentration of IL-1β was 0 ng/ml, the expression of BCRP mRNA in the 48 h and 72 h groups was higher than that in the 24 h group (n χ2=6.00, n P=0.034). Under the condition, when the concentration of IL-1β was 20 ng/ml(n χ2=8.00, n P=0.014) or 100 ng/ml(n χ2=6.50, n P=0.040), the expression of BCRP mRNA in the 72 h group was significantly higher than that in the 24 hours group. ④ When being stimulated for 72 hours, the expression of BCRP mRNA in the 100 ng/ml group was higher than that in the 0 ng/ml group (n χ2=12.00, n P=0.006).n Conclusion:Multidrug resistance mediated by BCRP exists in RA-FLS and may be associated with disease activity. IL-1β could regulate the expression of BCRP mRNA in FLS cells of RA patients, which may be time and concentration-dependent.