来氟米特对实验性变态反应性脑脊髓炎小鼠Th1/Th2平衡的影响

Effect of Leflunomide on the Balance of Th1 / Th2 in Experimental Allergic Encephalomyelitis Mice

目的探讨来氟米特(LEF)对实验性变态反应性脑脊髓炎(EAE)的防治作用及其可能的免疫学机制。方法将36只雌性C57BL/6小鼠依据随机数字表法分为大、小剂量LEF防治组及EAE对照组,每组12只。采用髓鞘少突胶质细胞糖蛋白35-55构建EAE模型。从造模前3 d开始起EAE对照组及大、小剂量LEF防治组分别予以生理盐水、LEF 8 mg/(kg·d)、2 mg/(kg·d)灌胃,连续10 d。观察小鼠发病情况及外周血中白细胞介素4(IL-4)、γ干扰素(IFN-γ)水平及其比值变化。结果与EAE对照组相比,LEF各防治组小鼠临床症状较轻,且外周血中IL-4、IL-4/INF-γ值增高(P<0.01),INF-γ水平显著降低(P<0.01),且与小剂量相比大剂量降低更明显。结论 LEF对EAE具有防治作用,且效果呈剂量依赖性。其防治作用可能与调节Th1/Th2比例平衡,Th0分化向Th1漂移有关。

Objective To investigate the effect of leflunomide（LEF） on experimental allergic encepha- lomyelitis（EAE） mice and the possible immunological mechanisms. Methods Total of 36 female C57BL/6 mice were randomly divided into large and small doses of LEF treatment group and the EAE control group, n = 12. Myelin oligodendrocyte glycoprotein 35-55 was used to build EAE model. From three days before the beginning of the control group and modeling large and small doses of LEF treatment group were fed saline, LEF 8 mg/（ kg ·d）, LEF 2 rag/（ kg ·d） for 10 days. Incidence and peripheral blood interleukin 4 （IL-4）, interferon γ （INF-γ） levels and ratios in the mice were observed. Results Compared with the control group, each LEF treatment group mice had mild clinical symptoms, and peripheral blood IL-4, IL-4/INF-γ values increased（P 〈 0.01 ）, INF-3, levels significantly reduced（ P 〈 0. 01 ）, and compared with the small doses LEF treatment group,high dose reduction was more significant. Conclusion LEF has preventive effect on EAE, and the effect is dose dependent. Its prevention and treatment may be associated with regulation of the balance of Th1/Th2 ,and ThO differentiation into Thl drift.