基于多药耐药基因P-糖蛋白表达研究温化蠲痹方治疗类风湿关节炎的增效机制  

Study on Mechanism of Incresing Clinical Effects of Treating Rheumatoid Arthritis by Wenhua Juanbi Recipe Based on Expression of P-Glycoprotein of Multiple Drugs Resistance Gene

作　　者：刘喜德[1] 杨梦霞[2] 叶丽红[1] 蔡龙[1] 周红娟[1] 王珊珊 杜静[1] 刘敏[2] 王安琪[2] 贺利群 

机构地区：[1]浙江省中西医结合医院关节病科,浙江杭州310003 [2]浙江中医药大学,浙江杭州310053

出　　处：《中华中医药学刊》2017年第11期2727-2731,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：浙江省自然科学基金项目(LY17H270004);浙江省中医药科技计划项目(2012ZB121;2013ZB096;2015ZA143);杭州市医药卫生科技计划项目(2010B027;2014A37);杭州市科技发展计划项目(20120633B12;20160533B45)

摘　　要：目的:观察温化蠲痹方治疗类风湿关节炎(RA)的临床疗效,研究其对RA患者耐药基因P-糖蛋白(P-g P)表达影响,探讨温化蠲痹方治疗RA的增效机制。方法:60例RA患者随机分为两组,中药温化蠲痹方加西药治疗组(治疗组)30例,对照组30例,其中对照组口服甲氨蝶呤片(MTX,每周1次,每次7.5 mg),来氟米特片(每天1次,每次10 mg),美洛昔康片(莫比可,每天2次,每次7.5 mg)。治疗组在口服上述西药的同时,加用温化蠲痹汤(每天1剂,分2次口服)治疗,观察12周。观察两组临床疗效,治疗前后症状、体征、实验室指标,包括中医症候疗效分析、健康状况评估(HAQ评分)、疾病活动指数(DAS28)、患者疼痛评估(VAS评分)、晨僵时间、血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP抗体)、血小板计数、P-g P表达、安全性指标等,运用实时定量PCR检测外周血P-g P表达。结果:治疗组总有效率(86.6%)优于对照组(76.6%),差异有统计学意义(P<0.05)。在改善DAS28、HAQ评分、VAS评分、关节肿胀数、关节压痛数、晨僵时间,与本组治疗前和对照组治疗后比较,差异均有统计学意义(P<0.05,P<0.01);两组患者P-g P、ESR、CRP、RF、抗CCP抗体、血小板计数等指标,与本组治疗前比较,差异均有统计学意义(P<0.05,P<0.01),治疗组治疗后上述指标改善优于对照组(P<0.05,P<0.01);两组出现肝酶升高、白细胞下降、胃肠道反应、感染及血压升高等,治疗组低于对照组,差异有统计学意义(P<0.05)。结论:中药温化蠲痹方加西药治疗RA疗效优于单独西药治疗,温化蠲痹方可降低RA患者多药耐药基因P-g P表达,改善患者对DMARDs多药耐药,可能是其治疗RA提高临床疗效机制之一,该方治疗RA患者安全、有效。Objective ： To observe the clinical effect of treating rheumatoid arthritis （RA） by Wenhua Juanbi Recipe （WJR） and study the expression of P - glycoprotein （ P - gP） of the drug resistance gene in patients with RA and discuss the mechanism of increasing effect of treating RA by WJR. Methods ： Sixty patients were randomly assigned to the control group and treatment group, 30 in each group. Both were treated with oral administration of methotrexate （ MTX, 7.5 mg per week）, Leflunomide （LEF, 10 mg,qd）, mebcicam （Mobic, 7.5 mg, bid）, but to the treatment group WJR was given additionally. The therapeutic course for both groups was 12 weeks. Clinical effect, changes of symptoms and physical signs and laboratory indices in 2 groups after treatment were observed. The expression of P - gP was detected by real - time quantitative PCR. Results ： The total effective rate in the treatment group was higher than that in the control group （86.6% vs 76.6% , P 〈 0.05）. The improvements in scores of symptoms and signs including DAS2$, HAQ scores, VAS score, joint swelling count, joint tenderness, morning stiff time and levels of laboratory indices （P -gP, anti -CCP antibody, RF, ESR, CRP, PLT and Ig） in the treatment group after treatment were significantly superior to those in the control group （ P 〈 O. 05 or P 〈 O. O1 ）. Occurring rate of elevated liver enzymes, white blood cells, gastrointestinal tract reaction, infection and blood pressure in the treatment group were lower than those of the control group（ P 〈 O. 05 ）. Conclusion：Effect of combined therapy of WJR and Western medicine is superior to that of using Western medicine alone in treating RA. WJR can reduce the expression of P - gP. Its mechanism of improving clinical effect for treating RA is possibly the inhibition on the expression of P - gP to improve multiple drugs resistance of DMARDs. WJR is safe and effective for treating RA.

关 键 词：温化蠲痹方 类风湿关节炎 多药耐药 P-糖蛋白 

分 类 号：R593.22[医药卫生—内科学]