目的:探讨雷公藤内酯醇治疗实验性自身免疫性脑脊髓炎(EAE)的免疫调节机制.方法:用MOG35-55肽段免疫C57/BL6小鼠,建立EAE动物模型.免疫后将小鼠随机分为治疗组和对照组,治疗组在开始发病后每天给予雷公藤内酯醇(100 μg/kg)治疗,对照组于同一天开始每天给予相同体积生理盐水,每天观察小鼠临床症状.疾病高峰期处死小鼠,HE染色检测脊髓炎性细胞浸润;ELISA检测血清中细胞因子含量,3H掺入法检测淋巴细胞增殖;FACS检测中枢神经系统中Th1/Th17和Treg细胞数量.结果:雷公藤内酯醇治疗能够缓解EAE发病,减轻中枢神经系统炎性细胞浸润;抑制EAE小鼠MOG特异性T细胞增殖;减少血清中炎症细胞因子含量;减少病灶处CD4+T 细胞IFN-γ和IL-17的分泌;上调CD4+T 细胞Foxp3的表达.结论:雷公藤内酯醇通过减少致病细胞Th1和Th17的浸润,增加Treg细胞的数量来治疗EAE.%Objective :To study the mechanism for triptolide treatment of expenmental autoimmune encephalomyelitis (EAE) .Methods :The EAE mouse model was established by immunization of mice with MOG35-55 peptide .The mice were randomly divided into treatment group and control group .The mice in treated group were administered triptolide (100 μg/Kg ) daily from disease onset .At the same time ,the control mice were administered normal saline .Mice were examined daily for disease symptoms according to the standard scale .Inflammatory infiltration of spinal cord tissue was examined by H&E staining .ELISA assay was used to detect contents of cytokines in serum .The proliferation of MOG-reactive T cells in tripotide-treated and control mice was investigated by 3H-TdR incorporation .The percentage of Th1 ,Th17 and regulatory T cells in MNCs derived from CNS was analyzed by flow cytometry .Results :Triptolide could ameliorate EAE symptoms .Histological evaluation of spinal cords showed that triptolide-treated mice had less infiltration of inflammatory cells .The proliferation of MOG-specific T cells from triptolide-treated mice and their inflammatory cytokine levels in serum decreased .Triptolide could reduce the secretion of IFN-γ and IL17 ,and meanwhile ,increase the expression of Foxp3 in CD4+ T cells from CNS of EAE mice .Conclusion :Triptolide has great therapeutic benefit in EAE by increasing the number of regulatory T cells and suppressing Th1 and Th17 cell development .
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