霉酚酸酯对实验性自身免疫性脑脊髓炎的治疗作用

Therapeutic effect of mycophenolate mofetil on autoimmune encephalomyelitis in Wistar rats

目的探讨霉酚酸酯(mycophenolate mofetil,MMF)对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)的治疗作用。方法采用豚鼠全脊髓匀浆和完全弗氏佐剂(CFA)为抗原,免疫Wistar大鼠复制急性EAE模型,给予MMF灌胃治疗,观察其对临床症状及病理学改变的影响。结果与EAE模型组相比,MMF治疗组的临床症状减轻,且迅速缓解,病程明显缩短。病理学观察显示EAE急性期中枢神经系统大量炎症细胞浸润,在血管周围形成"血管袖套"状结构,并向周围实质扩散,病变区可见明显的髓鞘脱失和轴突损伤;MMF治疗后病变范围及程度明显减轻。结论MMF对EAE大鼠具有明显的治疗作用,可有效控制EAE的临床病情,减轻中枢神经系统的病理损害。

Objective To investigate the therapeutic effect experimental autoimmune encephalomyelitis （EAE）. Methods of mycophenolate moletil （MMF） on rats with The guinea pig spinal cord homogenate （GP- SCH） and complete Freund＇ s adjuvant were used as the antigen to induce the acute EAE model in Wistar rats which were verified according to clinical scoring. Totally 36 rats were randomly and equally divided into 3 groups, that is, normal control, EAE group and MMF treatment group. In 10 d after immunization, normal saline or MMF （30 mg·kg^-1·d^-1 ） were given intragastrically for 7 d to the corresponding groups. The rats were sacrificed on the 16th day and 30th day after immunization for pathological changes of the brain and spinal cord. Clinical manifestation was scored during the experiment. Results Compared with the EAE model group, MMF-treated rats had lower clinical scores and shorter disease process. Besides, the inflammatory infiltration, demyelination and axonal damage in the central nervous system were significantly improved in MMF treatment group. Conclusion MMF is an effective drug in treating EAE, and can relieve the clinical signs and ameliorate pathological lesions in the central nervous system of acute EAE rats.