补肾解毒通络方对类风湿关节炎骨侵蚀影响的随机对照试验

Effect of Bushen Jiedu Tongluo Decoction on the Bone Erosion in Rheumatoid Arthritis:A Randomized Controlled Trial

目的观察补肾解毒通络方对活动期类风湿关节炎(RA)患者临床疗效及骨侵蚀的影响。方法将60例活动期RA患者随机分为治疗组30例,对照组30例。治疗组予补肾解毒通络方联合甲氨蝶呤治疗,对照组予单药甲氨蝶呤治疗,疗程6个月。记录治疗前后患者视觉模拟疼痛量表(VAS)评分、28处关节疾病活动度评分(DAS28)、关节压痛及肿痛数目、中医证候疗效评估、C反应蛋白(CRP)、血沉(ESR)等的变化,并通过超声影像观察补肾解毒通络方对RA患者骨侵蚀的影响,同时检测血清中炎症因子(IL-1、IL-6、IL-17、TNF-α)以及护骨素(OPG)、细胞核因子κB受体活化因子配体(RANKL)、OPG/RANKL的数值变化,并观察治疗过程中出现的不良反应。结果治疗组完成临床观察29例,对照组完成28例。与本组治疗前比较,两组DAS28、VAS评分、ESR、CRP、IL-17、TNF-α、RANKL水平降低,关节压痛数、关节肿胀数减少(P<0.05),OPG水平及OPG/RANKL升高(P<0.05),滑膜厚度、关节腔积液、滑膜内血流信号程度减少(P<0.05),治疗组IL-1、IL-6水平亦降低(P<0.05)。与对照组同期比较,治疗组治疗后DAS28、VAS评分、ESR、CRP、IL-17、TNF-α、RANKL水平降低,关节压痛数、关节肿胀数减少(P<0.05),中医证候治疗率及OPG/RANKL升高(P<0.05),滑膜厚度、关节腔积液、滑膜内血流信号程度减少(P<0.05)。治疗前骨侵蚀评分与炎症指标正明显相关,与OPG呈负相关,与RANKL呈正相关(P<0.05)。在治疗中无严重不良事件发生。结论补肾解毒通络方能有效改善RA患者临床表现,降低炎症指标,下调OPG/细胞核因子受体κB活化因子(RANK)/RANKL水平,在影像学上达到部分缓解,该方延缓骨侵蚀机制可能与抑制破骨细胞及炎症因子的活性有关。

Objective To investigate the effect of Bushen Jiedu Tongluo Decoction on the bone erosion in the patients with rheumatoid arthritis(RA).Methods Totally 60 patients with active RA were randomly assigned to treatment group(30 cases)and control group(30 cases).The treatment group was treated with Bushen Jiedu Tongluo Decotion combined with methotrexate,while the control group was treated with methotrexate.The course of treatment last for 6 months.The Visual Analog Scale(VAS)score,disease activity score in 28 joints(DAS28),the number of tenderness and swelling pain,the evaluation of Chinese medicine(CM)symptoms,and the level of CRP and ESR were recorded before and after treatment.The effects of bone erosion in patients with RA in two groups were observed by ultrasonography.Meanwhile,the changes of IL-1,IL-6,IL-17,TNF-α,osteoprotegerin(OPG),receptor activator of NF-κB ligand(RANKL)and OPG/RANKL were also measured.The adverse reactions during treatment were observed.Results After the treatment,29cases in the treatment group and 28 cases in the control group were completed.Compared with before treatment,the VAS,DAS28,the number of tenderness and swelling pain,and the level of ESR,CRP,IL-17,TNF-αand RANKL decreased in two groups(P<0.05),and the level of OPG and OPG/RANKL increased(P<0.05).Meanwhile,the synovial thickness,synovial effusion and intrasynovial blood flow signal also decreased(P<0.05).The level of IL-1 and IL-6 in the treatment group was lower than that before treatment(P<0.05).Compared with the control group,the VAS,DAS28,the number of tenderness and swelling pain,and the level of ESR,CRP,IL-17,TNF-αand RANKL decreased in treatment group after treatment(P<0.05),and effect ratio of CM symptoms and the level of OPG increased(P<0.05).The synovial thickness,synovial effusion and intrasynovial blood flow signal in the treatment group also lower than the control group(P<0.05).Bone erosion score before treatment was positively correlated with inflammatory indexes,negatively correlated with OPG,and positively correlated with RANKL(P<0.05).There were no serious adverse events occurred during the treatment.Conclusions Bushen Jiedu Tongluo Decoction could effectively improve the clinical manifestations of RA patients,reduce the level of inflammatory indicators and OPG/receptor outivator of NFκ-B(RANK)/RANKL levels,and achieve partial remission in imaging.The mechanism of delaying bone erosion may be related to prevent activities the osteoclast and inflammatory factor.