甲基强的松龙治疗实验性变态反应性脑脊髓炎的作用机制

目的:研究细胞因子、T细胞凋亡和淋巴细胞增殖在实验性变态反应性脑脊髓炎(EAE)形成中的作用及甲基强的松龙(MP)治疗EAE的作用机制。方法:采用人脑纯化的髓鞘碱性蛋白(MBP)与完全福氏佐剂免疫Lewis大鼠,建立EAE动物模型。用双抗体夹心ELISA法检测各组大鼠血清中IL-10、TNF-α、IFN-γ的含量:流式细胞仪检测外周血T细胞凋亡;3H-TdR释放法检测外周血淋巴细胞转化率。结果:与对照组比较,EAE组的外周血IFN-γ、TNF-α水平明显增高,IL-10水平明显降低,MP治疗后IFN-γ和TNF-α水平下降,IL-10浓度上调。MP还诱导外周血T细胞凋亡和抑制MBP致敏淋巴细胞增殖并呈剂量依赖性。结论:应用人MBP成功建立EAE大鼠模型,MP可能通过调节Th细胞因子格局、促进Th2细胞因子分泌、抑制MBP致敏淋巴细胞增殖及外周血T细胞凋亡而发挥治疗多发性硬化的作用。

The mechanism of methylprednisolone in the treatment of experimental allergic encephalomyelitis

Objective: To investigate the effects of cytokines, T cell apoptosis and lymphocytes proliferation in the production of experimental allergic encephalomyelitis ( EAE) and the mechanism of methylprednisolone ( MP) in the treatment of EAE. Methods: Lewis rats were selected and immunized by the purified myelin basic protein (MBP) extracted from human brain together with complete Freund adjuvant. The levels of IL-10,TNF-γand IFN-α in serum were detected by andwich E n SA. Peripheral T cell apoptosis was measured by means of flow cytometry. Lymphocytes proliferation was examined by 3H-thymidine autora-diography. Results: The contents of IFN-γ and TNF-α in the EAE group were significantly higher than those of the control group and the level of IL-10 was remarkably lower than those of the control group. After MP treatment, the concentrations of IFN-γ and TNF-α were down-regulated and the level of IL-10 were up-regulated. Peripheral T cell apoptosis was induced and MBP-specific lymphoproliferation was inhibited in a dose-dependent. Conclusions: The rat model of EAE was successfully produced. The mechanism of MP in the treatment of EAE may be through regulating Th cytokines profile, promoting a Th2 bias, inducing T cell apoptosis and inhibiting lymphoproliferation.