小白菊内酯对PD小鼠黑质区NF-κB和FLIP表达的影响  

Parthenolide modulates nuclear factor kappa B and FLICEinhibitory protein expression in substantia nigra of mice with MPTP-induced Parkinson's disease

作　　者：张辉[1] 张宇新[2] 魏子峰[2] 田清友[2] 张作凤[2] 孙明宏 王茜[2] 

机构地区：[1]唐山市第二医院关节病科,河北唐山063000 [2]河北联合大学基础医学院人体解剖学系,河北唐山063000

出　　处：《中国现代医学杂志》2015年第12期1-6,共6页China Journal of Modern Medicine

基　　金：河北省自然科学基金(No:C2004000689);河北省博士基金(No:05547008D-4);河北省科学技术与社会发展计划(No:04276135);唐山市科学技术研究与发展计划指令项目(No:13130267z);河北联合大学科学研究基金(No:Z201236);河北联合大学2013年大学生创新性实验计划(No:X2013034);2013年河北省大学生创新创业训练计划项目(No:201310081023)

摘　　要：目的探讨在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备的帕金森病(PD)小鼠模型中核因子NF-κB与FADD样白细胞介素1-转化酶样抑制蛋白(FLIP)之间的关系,研究核因子信号通路在PD发病中的作用机制。方法将C57BL/6N小鼠随机分为模型组、干预组和对照组。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酪氨酸羟化酶(TH)、NF-κB、FLIP和caspase-3的表达变化,以及给予小白菊内酯后对上述变化的影响。结果与对照组相比,模型组小鼠出现典型PD症状,TH阳性神经元明显丢失,蛋白水平下降,核因子信号通路被激活,其阳性表达明显增多,FLIP和caspase-3表达也明显增加;经小白菊内酯干预处理后,上述变化均减轻。结论核因子信号通路可能参与激活FLIP对PD模型小鼠黑质区凋亡有重要调控作用,小白菊内酯对PD模型小鼠有一定的神经保护作用。[Objective]To investigate the relationship between nuclear factor kappa B（NF-κB） and FLICE-inhibitory proteins（FLIP） in the substantia nigra（SN） of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP） induced Parkinson＇s disease（PD）, and to explore the possible mechanism of NF-κB signaling pathway in PD. [Methods]C57BL/6N mice were randomly divided into model group, inhibitor group and control group. Their behavioral changes were observed. Immunohistochemistry and Western blot were performed to detect the expressions of tyrosine hydroxylase（TH）, NF-κB, FLIP and caspase-3 in the SN and their changes following treatment with parthenolide, a specific inhibitor of NF-κB.[Results]Compared with the control mice, the mice with PD presented with typical symptoms of PD. In the model group, the number of TH-positive neurons was substantially reduced, the NF-κB signaling pathway was activated, the expression of NF-κB significantly increased; and the expressions of FLIP and caspase-3 also significantly increased. After parthenolide treatment, the expressions of NF-κB, FLIP and caspase-3 were obviously reduced as compared with those in the model group. [Conclusions]NF-κB signaling pathway may activate FLIP and regulate the apoptosis in the SN of the mouse model of subacute PD, and parthenolide may provide certain neuroprotective effect in PD model mice.

关 键 词：帕金森病 NF-ΚB FLIP CASPASE-3 小白菊内酯 

分 类 号：R742.5[医药卫生—神经病学与精神病学]