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三黄一龙汤加甲氨蝶呤对湿热痹阻型类风湿关节炎患者血清及关节液中肿瘤坏死因子α和干扰素γ的影响

Effect of Sanhuangyilong decoction plus methotrexate on tumor necrosis factor alpha and interferon gamma in serum and synovial fluid in rheumatoid arthritis patients with symptom pattern of damp heat obstruction.

作者信息

Liu Defang, Yan Jiao, Yun Mingdong, Yang Ming, Luo Yong, Zhang Jun, Guo Mingyang, Yang Mei, Yuan Weili, Zou Wei, Li Hua, Hu Yonghe

出版信息

J Tradit Chin Med. 2016 Oct;36(5):625-33. doi: 10.1016/s0254-6272(16)30082-6.

DOI:10.1016/s0254-6272(16)30082-6
PMID:29933531
Abstract

OBJECTIVE

To investigate the effect of Sanhuangyilong decoction plus methotrexate (MTX) on Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the serum and synovial fluid of rheumatoid arthritis (RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA.

METHODS

RA inpatients with damp-heat-obstruction symptom pattern (partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis (OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups: one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay (ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score in 28 joints (DAS28) were determined.

RESULTS

Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat- obstruction symptom pattern were higher than those in healthy control group (P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients (P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the synovial fluid of the osteoarthritis patients (P < 0.05). The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP, or DAS28 (P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant (P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant (P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR, CRP, and DAS28 in the combined group decreased compared with the before-treatment levels (P < 0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant (P > 0.05) compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28 (P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant (P < 0.01).

CONCLUSION

TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.

摘要

目的

探讨三黄抑龙汤联合甲氨蝶呤(MTX)对湿热痹阻证类风湿关节炎(RA)患者血清及关节液中干扰素γ(IFN-γ)和肿瘤坏死因子α(TNF-α)的影响,以及三黄抑龙汤、TNF-α和IFN-γ在RA发病中的作用。

方法

选取湿热痹阻证RA住院患者(部分伴有膝关节积液)作为研究对象。治疗前,将健康受试者和膝关节积液的骨关节炎(OA)患者分别纳入血清对照组和关节液对照组;治疗期间,将湿热痹阻证RA患者分为两组:一组为联合组,给予三黄抑龙汤联合MTX治疗;另一组为MTX组,仅接受MTX治疗。采用酶联免疫吸附测定(ELISA)法检测治疗前后血清及关节液中TNF-α和IFN-γ的表达水平,并测定外周血红细胞沉降率(ESR)、C反应蛋白(CRP)及28个关节疾病活动评分(DAS28)。

结果

治疗前,湿热痹阻证RA患者血清中TNF-α和IFN-γ水平高于健康对照组(P<0.05)。RA患者关节液中TNF-α和IFN-γ的表达水平高于RA患者血清中的表达水平(P<0.05)。RA患者关节液中TNF-α和IFN-γ的表达水平高于骨关节炎患者关节液中的表达水平(P<−0.05)。RA患者血清及关节液中TNF-α和IFN-γ的表达与炎症活动指标ESR、CRP或DAS28无相关性(P>0.05)。治疗2周后,联合组TNF-α和IFN-γ表达水平有所升高,但差异无统计学意义(P>0.05);相比之下,ESR、CRP和DAS28降低,差异有统计学意义(P<0.01)。治疗4周后,联合组TNF-α、IFN-γ、ESR、CRP和DAS28较治疗前降低(P<0.01)。治疗2周后,联合组TNF-α和IFN-γ表达水平与MTX组相比差异无统计学意义(P>0.05),但ESR、CRP和DAS28差异有统计学意义(P<0.05)。治疗4周后,联合组与MTX组相比,TNF-α, IFN-γ, ESR, CRP和DAS28差异有统计学意义(P<0.01)。

结论

TNF-α和IFN-γ可能参与RA的发病过程。湿热痹阻证RA患者采用三黄抑龙汤联合MTX治疗效果更佳,且优于单纯使用MTX治疗。

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