DNA聚合酶β抑制剂齐墩果酸对帕金森病小鼠模型的保护作用

The protective effect of oleanolic acid on dopaminergic neurons in a mouse model of Parkinson disease

目的观察DNA聚合酶β抑制剂齐墩果酸对帕金森病小鼠模型的保护作用。方法利用MPTP腹腔注射法制作小鼠帕金森病模型,在MPTP注射前后分别给予DNA聚合酶β抑制剂齐墩果酸干预,用免疫组织化学染色法检测小鼠中脑酪氨酸羟化酶(TH)阳性神经元,免疫印迹法检测中脑腹侧TH蛋白和活化的Caspase-3表达水平,HPLC法检测纹状体中多巴胺及其代谢产物的水平。结果小鼠腹腔注射MPTP后出现行为学异常,中脑黑质多巴胺能神经元损伤,中脑腹侧TH表达降低,活化的caspase-3水平增高,同时纹状体多巴胺及其代谢产物3,4-二羟基苯乙酸(DOPAC)水平降低。齐墩果酸干预能够显著改善小鼠的行为学评分,增加黑质多巴胺能神经元数量,抑制caspase-3活化,并增加纹状体多巴胺和DOPAC水平。结论齐墩果酸可能对帕金森病小鼠多巴胺能神经元具有保护作用。

Objective To investigate the effect of DNA polymeras inhibitor oleanolic acid on dopam inergic neurons in a mouse model of Parkinson disease （PD）,and provide evidence for the new treatment meth od of PD.Methods Intraperitoneal administrations of MPTP were delivered to mice at regular intervals to in duce Parkinsonism.Oleanolic acid,a DNA polymeras inhibitor were administrated before or after the injec tion of MPTP.The tyrosine hydroxylase （TH） positive neurons were stained with immunohistochemistry.The expression of TH and active caspas3 were determined by Western blotting.The concentration of dopa mine and its motabolite DOPAC were assessed by HPLC.Results After the administration of MPTP,the mice showed behavioral deficits,decreased number of dopaminegic neurons in the substantia nigra,decrased expression of TH,incrased expression of active caspas-3,and decrease of dopamine concentration in the stria tum.Oleanolic acid treatment attenuated behavioral deficits,dopaminergic neuronal death and striatal dopa mine depletion in the MPTP mouse model.Conclusions DNA polymerase β inhibitor oleanolic acid exerts neu roprotective effect against dopaminergic loss in a mouse model of Parkinson disease.