来氟米特对佐剂性关节炎大鼠的治疗作用及部分机制研究

摘要

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A771726体外对正常小鼠T细胞亚群的影响。结果 Lef(2,6与18 mg*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A771726(0.1，0.5，2.5，12.5，25，100 μmol*L-1)可抑制正常小鼠Con A诱导的Th细胞，对Con A诱导的Ts细胞无明显影响。而只有高浓度A771726(100 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。%AIM　To study the therapeutic action of leflunomide(Lef) on adjuvant arthritis (AA) rats and its mechanisms. METHODS　To observe the change of secondary inflammation,immune function on adjuvant arthritis(AA) rats treated with Lef and to detect the effect of A771726—the active product of Lef on T cell subgroup in mice in vitro.RESULTS　Lef(2,6,18 mg*kg-1×12 d) intragastric injection(ig) could signifcantly inhibit secondary reaction (secondary inflammatory swelling、 multiple arthritis) of AA rats.Lef couldnt effect the lowed response of Con A-induced splenolytes, and the decreased IL-2 synthesis in AA rats. But lef(2,6,18 mg*kg-1) could inhibit the elevated IL-1 released from peritoneal macrophage (PMΦ) in AA rats. A771726—the active product of Lef(0.1，0.5，2.5，12.5，25，100 μmol*L-1) could inhibit Con A-induced Th cells but has no effect in Con A-induced Ts cells in vitro.CONCLUSION　Lef has therapeutic action on AA rats which could be related to its immunosuppressory activities——mainly through inhibit cell-mediated immunity.