核因子NF-κB对帕金森病MPTP模型小鼠黑质区iNOS表达的影响

Influence of NF-κB on iNOS expression in substantia nigra of mouse models of Parkinson's disease induced by MPTP

①目的观察核因子NF-κB(nuclear factor kappa B)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备的帕金森病(PD)小鼠模型黑质区诱导型一氧化氮合酶(inducible nitricoxide,iNOS)表达的影响,以及给予人参皂甙Rg1(Ginsenoside Rg1,Rg1)后表达的变化,探讨在PD发病过程中NF-κB对iNOS的表达调控作用以及人参皂甙Rg1对PD可能的防治作用。②方法采用MPTP制备PD小鼠模型,观察小鼠行为学变化;采用免疫组织化学和免疫蛋白印迹法观察小鼠黑质区酪氨酸羟化酶(tyrosine hydroxylase,TH)、NF-κB和iNOS的表达变化;并观察给予人参皂甙Rg1后对上述变化的影响。③结果与对照组相比,模型组小鼠出现典型PD症状,黑质区TH阳性神经元明显丢失、蛋白水平下降,NF-κB和iNOS表达也明显增加,二者表达呈正相关关系;经人参皂甙Rgl处理后,上述变化均明显减轻。④结论在MPTP所致PD模型小鼠中,核因子NF-κB对黑质区iNOS表达可能起重要调控作用,人参皂甙Rg1可能通过影响NF-κB表达从而发挥对多巴胺能神经元的保护作用。

Objective To investigate effeetion of NF - KB in modulating the expression of iNOS in the substantia nigra （SN） of mice withl - methyl - 4 - phenyl - 1,2,3,6 - tetrahydrepyridine （MPTP） induced Parkinson＇ s disease （ PD）, and investi- gate the effect of ginsenoside Rgl on NF - KB to further explore the possible mechanism of the dopaminergic （DA） neuron death in PD. Methods C57BL/6N mice were treated with MPTP to produce the subaeute PD model, and the behavioral changes were ob- served. Immunohistoehemistry and Western blot for tyresine hydroxylase （TH） , NF - KB and iNOS were used to observe the changes of positive cell number in the midbrain after treatment with ginsenoside Rgl. Results Compared with the control mice, the mice with PD presented with typical symptoms of PD. The number of NF - KB, and iNOS positive cells significantly increased in the SN area （ P 〈 0.01 ）. The number of TH - positive neurons in the PD model group was substantially reduced （ P 〈 0.01 vs control group）. In mice with ginsenoside Rgl treatment, the number of NF - KB and iNOS positive cells was reduced obviously as compared with that in the model group （ P 〈0.01 ）. The number of TH - positive neurons in the SN was decreased by only 25% （ P 〈0.01 vs control group）. Conclusion NF - KB may play an important role in mediating iNOS expression in SN in the early stage of the MPTP - induced subaeute PD, and ginsenoside Rgl may influence the expression of NF - KB and protect the DA neurons in PD.