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目的 研究来氟米特 (Lef)对佐剂关节炎 (AA)大鼠的治疗作用。方法 观察佐剂性关节炎 (AA)大鼠给药后继发性足肿胀、免疫功能及前列腺素释放水平的变化 ,并检测Lef的活性产物A77172 6体外对正常小鼠T细胞亚群的影响。结果 Lef(2 ,6与 18mg·kg-1)灌胃给药 (ig)可明显抑制AA大鼠继发性的关节肿胀 ,改善AA大鼠多发性关节炎病变症状。对AA大鼠低下的ConA诱导的增殖反应和IL 2无明显影响 ,但对AA大鼠过高的IL 1产生有明显的抑制作用。体外培养发现Lef的活性产物A77172 6(0 1,0 5 ,2 5 ,12 5 ,2 5 ,10 0 μmol·L-1)可抑制正常小鼠ConA诱导的Th 细胞 ,对ConA诱导的Ts 细胞无明显影响。而只有高浓度A77172 6(10 0 μmol·L-1)对AA大鼠PMΦ产生的过高PGE2 有明显的抑制作用。结论 Lef具免疫抑制作用 ,通过抑制细胞免疫功能 ,实现对AA大鼠的治疗作用
Objective To study the therapeutic effect of leflunomide (AD) on adjuvant arthritis (AA) rats. Methods The changes of secondary foot swelling, immune function and prostaglandin release in adjuvant arthritis (AA) rats were observed. The effect of A77172 6, an active product of Lef, on the T lymphocyte subsets in normal mice was observed. Results Oral administration of Lef (2, 6 and 18 mg · kg-1) significantly inhibited secondary joint swelling and ameliorated the symptoms of multiple arthritis in AA rats. There was no significant effect of low ConA-induced proliferative response and IL-2 in AA rats, but significantly inhibited the excessive production of IL-1 in AA rats. In vitro, it was found that the active product of Lef A77172 6 (0 1, 0 5, 2 5, 12 5, 25, 10 0 μmol·L -1) inhibited ConA-induced Th cells in normal mice, No significant effect. However, only high concentration of A77172 6 (10 0 μmol·L-1) significantly inhibited the excessive PGE2 produced by PMΦ in AA rats. Conclusion Lef has immunosuppressive effect and can inhibit the cellular immune function and achieve the therapeutic effect on AA rats