CAJ | 학술논문

目的通过检测芳香烃受体(AhR)及其下游应答基因细胞色素P4501A1(CYP1A1)在类风湿关节炎(RA)患者外周血单个核细胞(PBMCs)内的表达水平,探讨AhR在RA中的意义.方法收集35名RA患者及20名健康对照者外周血,实时定量聚合酶链反应(RT-PCR)法测定PBMCsAhR mRNA和CYP1A1 mRNA的相对表达,采用流式细胞术测定AhR阳性细胞占PBMCs比例;分析来氟米特(LEF)治疗对AhR、CYP1 A1表达的影响;详细记录RA患者临床资料,计算疾病活动性评分,分析AhR、CYP1 A1的表达和AhR阳性细胞比例与临床指标的关系.结果 (1)RA患者非LEF治疗组PBMCs AhR mRNA相对表达高于健康对照组[(3.61±1.65)与(2.00±1.27),P=0.002],AhR阳性细胞比例高于健康对照组[(34.21±11.30)％与(18.83±7.32)％,P＜0.01];LEF治疗组与非LEF治疗组AhR mRNA相对表达差异无统计学意义[(3.83±1.62)与(3.61±1.65),P=0.670],AhR阳性细胞比例差异无统计学意义[(36.69±10.61)％与(34.21±11.30)％,P=0.462].(2)RA患者非LEF治疗组PBMCs内CYP1A1 mRNA相对表达高于健康对照组[1.33(0.08,7.86)与(0.62±0.29),z=-3.922,P＜0.01];LEF治疗组与非LEF治疗组CYP1A1 mRNA相对表达差异无统计学意义[(2.62±2.08)与1.33 (0.08,7.86),z=-0.133,P=0.894].(3)相关性分析:RA患者PBMCsAhR mRNA相对表达、AhR阳性细胞比例和CYP1A1 mRNA相对表达与血沉(ESR)、C反应蛋白(cRP)、抗环瓜氨酸肽(抗-CCP)抗体、DAS28评分、疾病病程均无相关性(P均＞0.05).结论 AhR在RA患者PBMCs内高表达,可能参与了RA的发病,但不能反映疾病活动性;AhR未被治疗剂量LEF激活,表达水平亦未受LEF影响.
목적 통과검측방향경수체(AhR)급기하유응답기인세포색소P4501A1(CYP1A1)재류풍습관절염(RA)환자외주혈단개핵세포(PBMCs)내적표체수평,탐토AhR재RA중적의의.방법 수집35명RA환자급20명건강대조자외주혈,실시정량취합매련반응(RT-PCR)법측정PBMCsAhR mRNA화CYP1A1 mRNA적상대표체,채용류식세포술측정AhR양성세포점PBMCs비례;분석래불미특(LEF)치료대AhR、CYP1 A1표체적영향;상세기록RA환자림상자료,계산질병활동성평분,분석AhR、CYP1 A1적표체화AhR양성세포비례여림상지표적관계.결과 (1)RA환자비LEF치료조PBMCs AhR mRNA상대표체고우건강대조조[(3.61±1.65)여(2.00±1.27),P=0.002],AhR양성세포비례고우건강대조조[(34.21±11.30)％여(18.83±7.32)％,P＜0.01];LEF치료조여비LEF치료조AhR mRNA상대표체차이무통계학의의[(3.83±1.62)여(3.61±1.65),P=0.670],AhR양성세포비례차이무통계학의의[(36.69±10.61)％여(34.21±11.30)％,P=0.462].(2)RA환자비LEF치료조PBMCs내CYP1A1 mRNA상대표체고우건강대조조[1.33(0.08,7.86)여(0.62±0.29),z=-3.922,P＜0.01];LEF치료조여비LEF치료조CYP1A1 mRNA상대표체차이무통계학의의[(2.62±2.08)여1.33 (0.08,7.86),z=-0.133,P=0.894].(3)상관성분석:RA환자PBMCsAhR mRNA상대표체、AhR양성세포비례화CYP1A1 mRNA상대표체여혈침(ESR)、C반응단백(cRP)、항배과안산태(항-CCP)항체、DAS28평분、질병병정균무상관성(P균＞0.05).결론 AhR재RA환자PBMCs내고표체,가능삼여료RA적발병,단불능반영질병활동성;AhR미피치료제량LEF격활,표체수평역미수LEF영향.
Objective To explore the significance of aryl hydrocarbon receptor (AhR) in patients with rheumatoid arthritis (RA) through detecting the levels of AhR and its response gene cytochrome P4501 A1 (CYP1 A1) in peripheral blood mononuclear cells (PBMCs).Methods Peripheral blood samples were collected from 35 patients with RA and 20 healthy subjects.The expression of AhR and CYP1A1 at mRNA level were detected by real-time PCR.The percentages of AhR-positive cells in PBMCs were detected by flow cytometry (FCM).The effects of leflunomide (LEF) on the expression of AhR and CYP1A1 were analyzed.The detailed clinical data of RA patients were recorded.The disease activity score (DAS) was calculated.Correlation analysis between AhR/CYP1A1 level and clinical data was conducted.Results (1) Both the expression of AhR at mRNA level and the percentage of AhR-positive cells in PBMCs from RA patients without LEF treatment were significantly higher than those from healthy subjects [(3.61±1.65) vs.(2.00±1.27),P=0.002; (34.21±11.30)％ vs.(18.83±7.32)％,P＜0.01].There were no statistically significant differences in the expression of AhR at mRNA level and the percentages of AhR-positive cells between patients with or without LEF treatment [(3.83 ± 1.62) vs.(3.61 ± 1.65),P =0.670 ; (36.69±10.61)％ vs.(34.21±11.30)％,P=0.462].(2) Non-LEF treatment group showed a higher relative expression of CYP1 A1 at mRNA level than that from control group [1.33 (0.08,7.86) vs.(0.62 ±0.29),z=-3.922,P＜0.01],but there was no statistical difference between LEF treatment group and non-LEF treatment group [(2.62±2.08) vs.1.33(0.08,7.86) z=-0.133,P=0.894].(3) Neither the expression of AhR and CYP1A1 at mRNA level nor the percentages of AhR-positive cells showed significant correlations with clinical data.Conclusion AhR was highly expressed in PBMCs from patients with RA,which might participate in the progression of rheumatoid arthritis.But the high expression of AhR did not reflect disease activity.Moreover,the treatment of LEF showed no significant influences on the expression of AhR and CYP1A1 in PBMCs from patients with RA.