小白菊内酯对帕金森病小鼠模型黑质多巴胺能神经元的保护作用  

Prthenolide protects dopaminegic neurons in the mouse model of Parkinson's disease

作　　者：王茜[1] 张辉[2] 刘名[3] 李琪佳[4] 孙明宏 田清友[1] 耿丽鑫 张乘云[1] 张宇新[1] 

机构地区：[1]河北联合大学基础医学院人体解剖学系 [2]唐山市第二医院关节一科 [3]唐山市协和医院骨科 [4]河北联合大学实验中心,唐山063000

出　　处：《神经解剖学杂志》2014年第3期357-362,共6页Chinese Journal of Neuroanatomy

基　　金：唐山市科学技术研究与发展计划指令项目(13130267z);河北联合大学科学研究基金(Z201236);2013年河北省大学生创新创业训练计划项目(201310081023);河北联合大学2013年大学生创新性实验计划(X2013034)

摘　　要：目的:探讨小白菊内酯在帕金森病小鼠模型中抑制核因子NF-κB(nuclear factor kappa B)信号通路对多巴胺(DA)能神经元的保护作用。方法:将C57BL/6N小鼠随机分为模型组、干预组和对照组。通过行为学、免疫组织化学和免疫蛋白印记法观察各组小鼠中脑黑质区酪氨酸羟化酶(TH)、核因子NF-κB、环氧合酶-2(COX-2)和半胱氨酸天冬氨酸蛋白酶-3(caspase-3)的表达变化情况。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,NF-κB、COX-2和caspase-3阳性细胞大量表达,蛋白水平显著升高(P<0.01)。抑制剂组小鼠上述变化明显减轻(P<0.01)。结论:在MPTP所致PD模型小鼠中,小白菊内酯通过抑制核因子NF-κB信号通路减少凋亡蛋白caspase-3表达,从而发挥神经保护作用。Objective： To investegate the protective effect of parthenolide on dopaminegic neurons apoptosis in the subatania nigra（SN） of MPTP-induced mouse model of Parkinson＇s disease （PD）, through inhibition of NF-κB. Methods： C57BL/6N mice were randomly divided into the model group, the inhibitor group and the control group, and the behavioral changes were observed. Immunohistochemistry and Western Blot for tyrosine hydroxylase （TH）, NF-κB, COX-2 and caspase-3 were used to observe the changes of positive cell number in the midbrain after treatment with parthenolide. Results ： Compared with the control mice, the mice with PD presented with typical symptoms of PD. The number of NF-κB, COX-2 and caspase-3 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 parthenolide treatment, the number of NF-κB, COX-2 and caspase-3 positive cells was reduced obviously as compared with that in the model group （P 〈0.01 ）. The TH-positive neurons in the SN after parthenolide treatment compared with the model group increased significantly（P 〈 0.01 vs control group）. Conclusion： In the mouse model of Parkinson＇s disease induced by MPTP, parthenolide may play a neural protection effect by inhibiting NF-κB to reduce the expression of caspase-3.

关 键 词：帕金森病 核因子 半胱氨酸天冬氨酸蛋白酶-3 环氧合酶-2 小白菊内酯 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]