目的:研究肿瘤坏死因子α(TNF-α)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,探讨其治疗EAE的作用机制。方法:选用雌性SJL/J小鼠95只,随机分为正常组、泼尼松3.9 mg·kg-1组、益肾达络饮20 g·kg-1组、益肾达络饮20 g·kg-1加泼尼松3.9 mg·kg-1组,从开始造模后7 d开始ig给药,连续15 d,从急性期、复发期采用免疫蛋白印迹法、免疫组化法测定EAE小鼠中枢神经组织中TNF-α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,泼尼松3.9 mg·kg-1组、益肾达络饮20 g·kg-1组、益肾达络饮20 g·kg-1加泼尼松3.9 mg·kg-1组中枢神经组织TNF-α表达水平明显降低(P〈0.05)。结论:降低TNF-α的表达水平,有助于缓解EAE病损程度;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;醋酸泼尼松和益肾达络饮调节TNF-α的表达水平可能是治疗EAE的机制之一。
Objective:To explore relationship of tumor necrosis factor α(TNF-α) with the clinical course in the central nervous system(CNS) of experimental autoimmune encephalomyelitis(EAE) in mice,and to explore the mechanism and effects of Yishen Daluo decoction(YDD) for treatment of EAE.Method:Ninety-five SJL/J mice were randomly divided into normal group,predinisone 3.9 mg·kg-1group,YDD 20 g·kg-1 group and YDD 20 g·kg-1 + predinisone 3.9 mg·kg-1 group.Immunohistochemistry and western blot were used to explore the expression of TNF-α in the CNS in SJL/J mice after 15 d administretion.Result:Compared with model group,YDD could reduce the relapse rate of EAE,improve the neurological function score(P < 0.05).Compared with model group,the content in central nervous system of TNF-α was reduced in normal group,predinisone-treated group,YDD group,predinisone-YDD complex treated group(P < 0.05).Conclusion:TNF-α mediated inflammatory cascade might play an important role in the mechanism of CNS inflammatory infiltration and axonal injury in EAE.Treatment with YDD can reduce the relapse rate of EAE,improve the neurological function score.The therapeutic mechanism of YDD is proposed by regulating the level of TNF-α.