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目的研究来氟米特对实验性变态反应性脑脊髓炎(EAE)的保护作用并探讨来氟米特的作用机制。方法将50只成年雌性豚鼠随机分为5组,各10只,分别为正常组、模型组与高中低3个剂量实验组。实验组分别给予来氟米特40,20,10 mg·kg-1·d-1(均3 m L),模型组和正常组均灌骨等量生理盐水。EAE诱导后,观察各组EAE发病率、潜伏期时间及神经功能障碍评分,用酶联免疫吸附法检测各组外周血白细胞介素-4(IL-4)及γ干扰素(IFN-γ)含量。结果与模型组及中、低2个剂量实验组相比较,高剂量实验组EAE发病率最低为40%(4/10),潜伏期时间最长为(14.8±3.8)d,神经功能障碍评分最低为(1.7±0.5)分(均P<0.05)。模型组,IL-4水平低于正常组,而IFN-γ高于正常组。与模型组比较,各实验组的IL-4水平明显增高,而IFN-γ明显降低,且呈剂量依赖性(均P<0.05)。结论来氟米特可降低EAE豚鼠发病率,减轻高峰期临床症状,对EAE大鼠发病具有保护作用。
Objective To study the protective effect of leflunomide on experimental allergic encephalomyelitis (EAE) and to explore the mechanism of leflunomide. Methods Fifty adult female guinea pigs were randomly divided into 5 groups and 10 rats in each group, which were normal group, model group and high school and low dose group. The experimental group were given leflunomide 40,20,10 mg · kg-1 · d-1 (all 3 m L), the model group and the normal group were bile equal amount of saline. After EAE induction, the incidence of EAE, latency time and neurological dysfunction score were observed in each group. The levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in peripheral blood of each group were detected by enzyme-linked immunosorbent assay . Results The lowest incidence of EAE was 40% (4/10) and the longest incubation period was (14.8 ± 3.8) days in EAE group and lowest in EAE group (1.7 ± 0.5) points (all P <0.05). The level of IL-4 in the model group was lower than that in the normal group, while the level of IFN-γ in the model group was higher than that in the normal group. Compared with the model group, the levels of IL-4 in each experimental group were significantly increased, while IFN-γ was significantly decreased and in a dose-dependent manner (all P <0.05). Conclusion Leflunomide can reduce the incidence of EAE guinea pigs, reduce the peak clinical symptoms, protect the pathogenesis of EAE rats.