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

目的研究知母活性成分ZMR在慢性1-甲基4-苯基-1，2，3，6-四氢吡啶（MPTP）损伤拟帕金森病小鼠模型中对脑内多巴胺转运蛋白（DAT）及多巴胺（DA）代谢的影响。方法将C57BIV6小鼠分为4组：对照组、模型组、ZMR低剂量组和ZMR高剂量组。除对照组注射生理盐水外，其他3组小鼠按体质量腹腔注射丙磺舒250mg／kg，0．5h后按体质量皮下注射MPTP 15mg／kg，每周注射2次，连续5周，共计10次。低剂量组按体质量灌胃给予ZMR 10mg／kg，高剂量组给予ZMR 26mg／kg，每日1次，造模开始后1周起连续给药60d。采用DAT放射自显影、单胺氧化酶B（MAO—B）活力测定和DA及其代谢产物的高效液相色谱法测定等方法研究ZMR在慢性MPTP损伤小鼠模型中对脑内DA失活的作用。采用SAS6.12软件，多组间比较采用单因素方差分析，两组间的比较采用团体Student’s t检验。结果与模型组（10．3±0．9）U／mg蛋白]比较，ZMR低剂量组（10．6±0．8）U／mg蛋白]和高剂量组（10．7±0．9）U／mg蛋白]的脑内MAO—B活力无显著改变（F=0．0717，P〉0．05）；而DAT密度分别从0．212±0．012增加到0．268±0．019和0．281±0．018，分别增加了26．42％和32．55％（t=2．5314和3．1124，P〈0．05和〈0．01）；每克纹状体内的DA质量分别从（3．00±0．25）μg/g增加到（4．21±0．32）μg／g和（4．58±0．39）μg／g，分别提高了40．04％和52．29％（t=2．9879和3．4163，P〈0．05和〈0．01）。小鼠每克纹状体内DA质量与DAT密度呈明显正相关（r=0．6833，P〈0．01）。结论ZMR能提高慢性MPTP损伤小鼠模型的纹状体DA水平，这种作用与DA降解无关，与提高DAT密度有关。

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

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.