目的:研究p38丝裂原活化蛋白激酶(p38MAPK)信号转导通路在实验性自身免疫性脑脊髓炎(EAE)发病中的作用,观察中药复方益肾达络饮干预EAE的疗效,探讨益肾达络饮治疗EAE的作用机制。方法:采用免疫蛋白质印迹法、免疫组化法测定EAE小鼠CNS中p38、p-p38蛋白表达的变化。结果:益肾达络饮能降低EAE的复发率(P〈0.05),改善EAE模型小鼠神经功能评分(P〈0.05)。与模型组相比,抑制剂SB203580组、激素组、中药组、中药加激素组p-p38表达水平明显降低(P〈0.05)。结论:p38MAPK介导的炎性级联反应是EAE小鼠CNS炎性浸润,轴索损伤的重要原因;益肾达络饮能降低EAE的复发率,有效改善EAE小鼠神经功能损伤;中药益肾达络饮干预EAE的作用机制与对p38MAPK信号通路的调节密切相关。
Objective: To investigate p38MAPK relationship with the clinical course in the CNS of EAE mice,and investigate the mechanism of Yishen Daluo Decoction,to explore the efficiency of Yishen Daluo Decoction,on treated experimental autoimmune encephalomyelitis.Methods: Immunohistochemistry and Western Blot were used to explore the expression of p38,p-p38 in the CNS of SJL mice.Results: Compared with model group,Yishen Daluo Decoction treatment of EAE can reduce the relapse rate of relapse-remitting EAE mice,improve the neurological function score(P0.05).Compared with model group,the content in central nervous system of p-p38 was reduced in normal group,model group,hormone-treated group,SB203580-treated group,Yishen Daluo Decoction-treated group,hormone-Yishen Daluo Decoction complex treated group.Conclusion: Treatment with Yishen Daluo Decoction can reduce the relapse rate of relapse-remitting EAE mice,improve the neurological function score.p38MAPK-mediated inflammatory cascade might play an important role in the mechanism of CNS inflammatory infiltration and axonal injury in EAE.The therapeutic merchanism of Yishen Daluo Decoction was proposed by regulating the signal path of p38MAPK.