淫羊霍苷通过Nurr1抑制炎症缓解帕金森症小鼠多巴胺能神经元损伤

Icariin ameliorates dopaminergic neuron lesion though Nurr1 dependent inflammation inhibiting

目的探讨淫羊藿苷是否通过核受体相关蛋白1(Nurr1)影响帕金森症(PD)小鼠黑质炎症及对多巴胺能神经元的保护作用。方法24只雄性C57BL/6小鼠随机分为对照组(Con组)、PD模型组(MPTP组)、单纯淫羊藿苷组(ICA组)及淫羊藿苷治疗组(ICA+MPTP组)。ICA组及ICA+MPTP组给予ICA(60 mg/kg灌胃,3周),在第3周,给予MPTP组及ICA+MPTP组MPTP(30 mg/kg,腹腔注射,1周),Con组给予等量生理盐水。免疫组化检测黑质区域Nurr1表达;免疫荧光检测黑质区域星形胶质细胞、小胶质细胞及多巴胺能神经元数量;免疫蛋白印迹法检测黑质组织Nurr1、TNF-α、IL-1β及IL-6表达水平。结果MPTP组Nurr1表达水平明显低于Con组,而ICA+MPTP组Nurr1水平较MPTP组升高;ICA可明显缓解由MPTP诱导的星形胶质细胞及小胶质细胞数量的升高;ICA可抑制MPTP诱导的黑质区域炎症因子TNF-α、IL-1β及IL-6的上调;ICA可缓解MPTP诱导的黑质区域多巴胺能神经元的减少。结论ICA可通过Nurr1抑制黑质区域星形胶质细胞及小胶质细胞的数量增加,并抑制其炎症因子的表达,保护黑质区域多巴胺能神经元。

Objective To investigate whether icariin affected substantia nigral inflammation through nuclear receptor associated protein 1(Nurr1)and protected dopaminergic neurons in Parkinson's disease(PD)mice.Methods Twenty four male C57BL/6 mice were randomly divided into control group(Con group),PD model group(MPTP group),icariin group(ICA group)and icariin treatment group(ICA+MPTP group).ICA group and ICA+MPTP group were administrated ICA(60 mg/kg gavage,3 weeks)in the third week.MPTP group and ICA+MPTP group were administrated MPTP(30 mg/kg,intraperitoneal injection,1 week),while the Con group was administrated with the same amount of normal saline.Immunohistochemistry was used to detect the expression of Nurr1 in the substantia nigra.Immunofluorescence was used to detect the number of astrocytes,microglia and dopaminergic neurons in substantia nigra.Western blotting was used to detect the expression of Nurr1,TNF-α,IL-1βand IL-6 in substantia nigra.Results The level of Nurr1 in MPTP group was significantly lower than that in con group,while that in ICA+MPTP group was significantly higher than that in MPTP group.ICA significantly alleviated the increase of astrocytes and microglia induced by MPTP.In addition,ICA inhibited the up regulation of TNF-α,IL-1βand IL-6 induced by MPTP and alleviated the decrease of dopaminergic neurons induced by MPTP.Conclusion ICA could protect dopaminergic neurons in substantia nigra by inhibiting the increase of astrocytes and microglia in substantia nigra and the expression of inflammatory factors through Nurr1.