目的观察不同比例甘草配伍祖师麻对大鼠佐剂性关节炎(AA)模型的治疗作用,筛选两者配伍比例,探讨其配伍意义。方法采用足跖皮内注射弗氏完全佐剂制备AA模型,将140只模型大鼠随机分成14组:模型组,雷公藤多苷片组,祖师麻低、中、高剂量组,甘草低、中、高剂量组,祖师麻-甘草(3:1)低、中、高剂量组,祖师麻.甘草(3:2)低、中、高剂量组,另取10只正常大鼠为对照组,给药组大鼠造模前2d开始ig给药,连续给药31d,观察各组大鼠体质量变化,计算足肿胀度、关节炎指数(AI),采用ELISA法检测大鼠血清炎症细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平,观察大鼠膝关节组织病理变化,通过免疫组化法测定大鼠膝关节滑膜组织中血管内皮生长因子(vEGF)、巨噬细胞游走抑制因子(MIF)的表达。结果与模型组比较,祖师麻组、祖师麻甘草配伍组能够明显抑制AA大鼠体质量减轻的趋势,对抗AA大鼠足肿胀度及AI的增加,降低异常升高的血清TNF-α、IL-1β水平,改善关节病理组织变化,减少滑膜组织VEGF、MIF的表达,其中以祖师麻.甘草(3:2)配伍组效果最优。结论祖师麻甘草配伍后,对AA大鼠各项指标改善作用显著,作用优于单用祖师麻,其最佳配伍比例为祖师麻-甘草(3:2)。调节血清炎症细胞因子TNF-α、IL-1β及滑膜组织VEGF、MIF的表达,可能是祖师麻甘草配伍治疗类风湿性关节炎机制之一。
Objective To study the therapeutic effects of different compatibility of Daphnes Giraldii Cortex (DGC) and Glycyrrhizae Radix et Rhizoma (GRR) on rat adjuvant-induced arthritis (AA) model, to screen the compatibility ratios, and to explore the possible mechanism. Methods AA model in SD rats was established, then the arthritic rats were randomly divided into 14 groups such as model, Tripterygium Glycosides Tablet (TGT), low-, mid-, high-dose DGC, low-, mid-, high-dose GRR, low-, mid-, high-dose DGC + GRR (3 : 1), and low-, mid-, high-dose DGC + GRR (3 : 2) groups, and 10 normal rats were as control group. The rats in treatment groups were ig administered 2 d before the model establishment, for 31 d. The body weight changes were observed, the paw edema and arthritis index (AI) were calculated, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in AA rat serum were detected by ELISA. The expression levels of VEGF and MIF were detected with immunohistochemistry. Results DGC + GRR, and DGC significantly.inhibited the decrease of body weight, also reduced paw swelling, AI, levels of TNF-α and IL-1β in AA rat serum, joint damages of AA rats, and levels of VEGF and MIF in the synovial membrane of AA rats, and the DGC + GRR (3 : 2) group had the best effect. The differences were significantly compared with the model group (P 〈 0.05, 0.01). Conclusion The combined use of DGC and GRR can obviously relieve the arthritis syndrome in AA rats by reducing the expression of serum cytokines as well as inhibiting the joint damage, and its therapeutic effect is better than used separately. Furthermore, the curative effect is the best when the compatibility ratio of DGC and GRR reaches 3 : 2. Reducing TNF-α and IL- 1β contents in serum and the levels of VEGF and MIF in synovial membrane may be the mechanism of drug treatment of rheumatoid arthritis.