知母活性成分ZMR对慢性帕金森病模型小鼠多巴胺系统的调节

objective The significant neuropathological features of Parkinson's disease include sharp decrease of striatal dopamine (DA) and downregulation of striatal dopamine transporter (DAT) density in nigrostriatal pathway.The purpose of this research was to investigate the effects of ZMR on the DAT and DA membolism in the brain of a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinisen's disease.Metbods C57BL/6 mice were divided into four groups:control mice,model mice,model mice treated with 10 mg/kg of ZMR(ZMR-10)and model mice treated with 26 mg/kg of ZMR(ZMR-26).All mice except control received ten doses of MPTP(15 mg/kg,subcutaneous injection)plus probeneeid(250 ms/kg,intraperitoneal injection)twice a week in five weeks.Mice in groups of ZMR10 and ZMR-26 were administrated 10mg/kg and 26 mg/kg of ZMR by oral gavage once daily for 60 d respectively.Striatal DAT was detected by autoradiography using 125I-2β-carbomethoxy-3B-(4-iodophenyl)-N-(3-fluoropropropyl) nortropane (FP-CIT).Monoamine oxidase B(MAO-B)activity was determined with a commercial kit.DA and its metabolites were determined by high performance liquid chromatography-electrochemical detection(HPLC-ECD).Staffstical analysis was performed with SAS 6.12 software,and the oneway ANOVA,grouped t-test Were used to analyze the data.Results Compared with vehicle treated model mice,ZMR-10 and ZMR-26 increased striatal DAT density from 0.212±0.012 to 0.268±0.019 and 0.281±0.018 respectively(t=2.5314,3.1124,P＜0.05 and＜0.01 respectively),raised striatal DA levels from(3.00±0.25)μg/g to(4.21±0.32)μg/g and(4.58±0.39)μg/g respectively(t=2.9879,3.4163.P＜0.05 and＜0.01 respectively).However.ZMR-10 and ZMR-26 did not affect the MAO-B activity.Conclusion ZMR raises striatal DA levels in chronic MPTP-model mice.which is closely related to the elevation of striatal DAT density but not related to catabolism of DA.

Regulation of a sapogenin from Rhizoma Anemarrhenae,ZMR on dopaminergic system in a chronic model of Parkinson's disease