摘要
目的:研究核因子(NF-κB)在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(PD)模型中的影响和对环氧合酶-2(COX-2)的表达调控作用以及人参皂甙Rg1对其的影响,探讨导致多巴胺(DA)能神经元变性失活的可能机制.方法:采用MPTP制备亚急性PD小鼠模型,用免疫组织化学法和免疫蛋白印迹法观察小鼠黑质区酪氨酸羟化酶(TH),COX-2,前列腺素E2(prostaglandine2,PGE2)以及NF-κB的表达变化;并观察给予人参皂甙Rg1对上述变化的影响.结果:与对照组小鼠相比,模型组小鼠出现典型PD症状,在MPTP第5次注射后24h,黑质区NF-κB(34.6±5.6),COX-2(28.2±5.1),PGE2(36.1±4.2)阳性细胞较对照组NF-κB(2.5±0.8),COX-2(1.0±0.3),PGE2(3.2±0.4)阳性细胞显著增加(P<0.01),TH阳性神经元显著丢失60%(P<0.01);经人参皂甙Rg1处理后,模型组小鼠PD症状减轻,与模型组比较,黑质区NF-κB(4.9±2.1),COX-2(1.9±0.7),PGE2(4.6±0.3)阳性细胞明显减少(P<0.01),TH阳性细胞数较对照组仅下降32%.结论:核因子NF-κB在亚急性PD模型早期对黑质COX-2表达中可能起重要调控作用;人参皂甙Rg1可能影响NF-κB及C0X-2表达而对小鼠多巴胺神经元起一定保护作用.
AIM： To investigate the effect of NF-κB on the expression of cyclooxygenase-2（COX-2） in substantia nigra（SN） of the mouse models of Parkinson＇s disease （PD） induced by 1-meth- yl-4-phenyl-1,2, 3,6-tetrahydropyridine（MPTP） and investigate the influence of ginsenoside Rgl on NF-κB to further explore the possible mechanism of the dopaminergic （DA） neuron death in PD. METHODS： C57BL/6N mice were administrated with MPTP to produce subacute PD models. PD mice were observed in behavioral changes. Immunohistochemistry and Western Blot for tyrosine hydroxylase （ TH）, COX-2, prostaglandine 2 （ PGE2 ） and NF-κB were used to observe the changes of positive cell number in the midbrain and the changes after treated with ginsenoside Rgl. RESULTS： Compared with the mice in control group, the model mice represented the typical symptoms of PD. The numbers of NF-κB（34.6 ±5.6）, COX-2（28.2 ±5.1）, PGE2（36.1 ±4.2） immunoreactive cells were significantly increased in SN area at 24 h after the 5 th injection of 30 mg/kg MPTP（P 〈0.01 ） compared with the numbers of NF-κB （ 2.5± 0.8 ）, COX-2 （ 1.0 ± 0.3 ）, PGE2 （3.2 ± 0.4 ） immunoreaetive ceils in control group . The number of TH-positive neurons in model group was distinctly reduced by about 60% （ P 〈 0. 01 ）. In ginsenoside Rgl treated group, the numbers of NF-κB（4.9 ±2.1 ）, COX-2（ 1.9 ±0.7）, PGE2（4.6 ±0.3） positive cells were reduced obviously as compared with the model group（P 〈0.01 ） , and the number of TH- positive neurons in SN was only decreased by 32% （ P 〈 0.01 vs control group）. CONCLUSION： NF-κB may play an important role in mediating COX-2 expression in SN in the early stage of the MPTP-induced subacute PD, and ginsenoside Rgl may influence the expression of NF-κB and protect the DA neurons in PD.
出处
《第四军医大学学报》
北大核心
2008年第19期1757-1760,共4页
Journal of the Fourth Military Medical University
基金
河北省自然科学基金(C2004000689)
河北省博士科研基金(05547008D-4)
