目的

评价尪痹胶囊联合来氟米特治疗湿热阻络型类风湿关节炎（RA）的疗效及治疗前后血清巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子-α（TNF-α）、T细胞亚群等变化。

方法

前瞻性选择河北北方学院附属第一医院风湿免疫科2022年2月至2023年10月90例符合《中国类风湿关节炎诊疗指南》中RA诊断标准且中医辩证为湿热阻络证的患者作为研究对象；排除对甲氨蝶呤药物治疗不耐受者，患有对本研究观察指标有影响的疾病患者，或近期接受过生物制剂或免疫抑制剂治疗，对本研究药物有禁忌症者。采用随机数字表法分为2组，对照组45例采取来氟米特治疗12周，观察组45例在此基础上加用尪痹胶囊。比较两组治疗前、治疗12周后检测血清GM-CSF、TNF-α、T细胞亚群、视觉模拟评分（VAS）、28个关节疾病活动度评分（DAS28）、压痛关节数、肿胀关节数、红细胞沉降率（ESR）、C反应蛋白（CRP），并评价疗效。非正态分布的计量资料用M（P₂₅，P₇₅）描述，采用秩和检验；正态分布的计量资料用（±s）描述，采用t检验。

结果

治疗12周后两组VAS评分、DAS28、压痛关节数和肿胀关节数均低于治疗前，GM-CSF、TNF-α、ESR、CRP水平均低于治疗前，差异有统计学意义（观察组t=7.206、5.402、16.808、8.153、17.283、15.279、22.604、20.716， 对照组t=4.826，3.282、9.117、6.305、5.279、9.462、9.206、8.715，均为P<0.05）；且观察组治疗12周后VAS评分、DAS28评分、压痛关节数、肿胀关节数、GM-CSF、TNF-α、ESR、CRP水平及差值均低于对照组，差异有统计学意义（t=3.782、3.827、4.280、4.106、8.226、9.254、6.118、5.742，差值t=4.193、4.106、5.394、4.908、9.240、10.143、7.506、11.628，均为P<0.05）。治疗12周后两组主症（关节肿胀、伸屈不利、晨僵、发热）积分均低于治疗前，观察组次症（口渴、小便黄、大便干燥）积分均低于治疗前（观察组Z=11.076、9.359、9.517、4.938、5.014、4.017、4.362， 对照组Z=4.271、5.824、4.293、4.156，均为P<0.05）。观察组治疗12周后主症和次症积分及差值均低于对照组，差异有统计学意义（Z=7.626、3.527、4.942、3.642、7.282、4.722、1.916；差值Z=7.620、3.426、4.728、3.517、7.406、4.826、4.806，均为P<0.05）。治疗12周后观察组CD3⁺、CD4⁺、自然杀伤（NK）细胞、CD4⁺/CD8⁺比值均高于治疗前，CD8⁺低于治疗前；且观察组治疗12周后白细胞抗原分化簇（CD）3⁺、CD4⁺、NK细胞、CD4⁺/CD8⁺比值及差值均高于对照组，CD8⁺绝对值及差值均低于对照组，差异有统计学意义（观察组t=24.806，17.443，16.624，22.550，15.744；组间水平 t=9.557、9.127、7.014、8.146、7.682；组间差值t=10.529，9.280，8.106，9.280，8.206； 均为P<0.05）。观察组不良反应发生率为13.3%，对照组为15.6%，差异无统计学意义（χ²=0.683，P>0.05）。

结论

尪痹胶囊联合来氟米特可降低湿热阻络型RA患者的免疫炎症反应，减轻关节疼痛和主、次症，提高疗效，且不增加不良反应。

Objective

To evaluate the efficacy of Wangbi Capsules combined with leflunomide in treating rheumatoid arthritis (RA) of the damp-heat obstruction type and the changes in serum granulocytemacrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-α), T cell subsets, etc.before and after treatment.

Methods

A total of 90 patients in the Rheumatology and Immunology Department of the First Affiliated Hospital of Hebei North University from February 2022 to October 2023 who met the diagnostic criteria for RA in the Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis in China and whose traditional Chinese medicine (TCM) dialectical theory was damp-heat blocking collateralcollateral syndrome were selected as the study objects.Patients who were intolerant to methotrexate therapy，recently received biologic agents or immunosuppressant treatment, with contraindications to the drugs of this study and had diseases affecting the observational indicators of this study were excluded.The enrolled patients were divided into two groups by random number table method, 45 cases each.The control group were treated with leflunomide for 12 weeks, and the observation group additionally accepted Zobi capsules based on this treatment.Serum GM-CSF, tTNF-α, T cell subsets, visual analogue sale (VAS), 28 joint disease activity score(DAS28), number of tenderness joints, number of swollen joints, erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) were compared between the two groups before treatment and 12 weeks after treatment.The main disease and secondary disease scores were statistically analyzed.The measurement data of nonnormal distribution were described by M (P₂₅, P₇₅) and rank sum test was used.The measurement data of normal distribution are described by (±s) and t test was used.

Results

After 12 weeks of treatment, VAS score,DAS28, number of tender joints and swelling joints in both groups were lower than before treatment; the levels of GM-CSF, TNF-α, ESR and CRP were all lower than the data before treatment, and the differences were statistically significant (observation group t=7.206, 5.402, 16.808, 8.153, 17.283, 15.279, 22.604, 20.716;control group t=4.826, 3.282, 9.117, 6.305, 5.279, 9.462, 9.206, 8.715, all P<0.05); After 12 weeks of treatment, VAS score, DAS 28 score, number of painful joints, number of swollen joints, GM-CSF, TNF-α,ESR, CRP levels and score differences in the observation group were lower than those in the control group, and the differences were statistically significant (t=3.782, 3.827, 4.280, 4.106, 8.226, 9.254, 6.118, 5.742;score differences t=4.193, 4.106, 5.394, 4.908, 9.240, 10.143, 7.506, 11.628; all P<0.05).After 12 weeks of treatment, the scores of main symptoms (joint swelling, adverse extension and flexion, morning stiffness and fever) in both groups were lower than before treatment; the scores of secondary symptoms (thirst, yellow urine,dry stool) in the observation group were lower than the data before treatment (observation group Z=11.076, 9.359,9.517, 4.938, 5.014, 4.017, 4.362; control group Z=4.271, 5.824, 4.293, 4.156; all P<0.05).After 12 weeks of treatment, the scores and differences of the main symptoms and secondary symptoms of the observation group were lower than those in the control group, and the differences were statistically significant (Z=7.626,3.527, 4.942, 3.642, 7.282, 4.722, 1.916; score differences Z=7.620, 3.426, 4.728, 3.517, 7.406, 4.826,4.806; all P<0.05).After 12 weeks of treatment, the ratios of cluster differentiation (CD)3⁺, CD4⁺, natural killer(NK) cells and CD4⁺/CD8⁺ in observation group were higher than before treatment, and CD8⁺ was lower than before treatment; after 12 weeks of treatment, the ratios and differences of CD3⁺, CD4⁺, NK cells and CD4⁺/CD8⁺in the observation group were higher than those in the control group, and the absolute values and differences of CD8⁺ were lower than those in the control group (observation group t=24.806，17.443，16.624，22.550，15.744；inter-group level t=9.557, 9.127, 7.014, 8.146, 7.682； difference between groups t=10.529，9.280，8.106，9.280，8.206；all P<0.05).The incidence of adverse reactions was 13.3% in the observation group and 15.6% in the control group, and the difference was not statistically significant (χ²=0.683, P>0.05).

Conclusion

Wangbi Capsules combined with leflunomide can reduce the immune inflammatory response in patients with damp-heat obstruction type RA, alleviate joint pain and primary and secondary symptoms, improve curative effect, and do not increase adverse reactions.