Genistein对Parkinson病模型小鼠黑质纹状体通路的保护作用  

The protective effect of genistein on nigrostriatal pathway in the mouse model of Parkinson ’s disease

作　　者：刘黎星[1] 徐丽[1] 陈文芳[1] 

机构地区：[1]青岛大学医学院生理学教研室,青岛266071

出　　处：《神经解剖学杂志》2008年第5期543-547,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(No30570573);山东省教育厅(J05L01)资助项目

摘　　要：为了研究大豆异黄酮活性成分genistein对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备的去卵巢(OVX)Parkinson病(PD)模型小鼠黑质纹状体通路的保护作用,我们将OVX PD小鼠随机分为对照组、MPTP组、genistein预处理组和雌激素预处理组,采用免疫组织化学染色结合逆转录-聚合酶链式反应法(RT-PCR)检测黑质致密带(SNpc)神经元酪氨酸羟化酶(TH)的表达情况,采用高效液相色谱法(HPLC-ECD)检测小鼠纹状体(Str)多巴胺(DA)及其代谢物二羟基苯乙酸(DOPAC)和高香草酸(HVA)的含量。结果显示:Genistein及雌激素用药组SN内TH阳性神经元数量及THmRNA的表达水平较MPTP组显著升高(P<0.01)。MPTP组Str内DA及其代谢产物DOPAC和HVA的含量较对照组明显降低(P<0.01)。genistein及雌激素用药组Str内DA、DOPAC及HVA含量较MPTP组显著升高(P<0.01)。上述结果提示genistein对MPTP制备的PD模型小鼠黑质DA能神经元有明显的保护作用。To investigate the neuroproteetive effect of genistein, the active ingredient from soy isoflavone, on dopaminergic neurons of ovariectomized （OVX） 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） -induced PD model mice, C57 BL6 mice were ovariecto- mized and treated with genistein （10mg/kg） intraperitoneally （i. p.） or estradiol benzoate （50μg/kg, i. p. ） for 3 d prior to MPTP injection. Immunohistochemistry was used to assess the number of tyrosine hydroxylase-immunoreactive （TH-IR） neurons in the substantia nigra pars compacta （SNpc）. Reverse transcfiption-polymerase chain reaction （RT-PCR） was used to determine the gene expressions of TH in the SN. The contents of dopamine （DA） and its metabolites dihydroxy-phenylacetic acid （DOPAC） and homovanillic （HVA） in the stria-turn （Str） were determined by using high performance liquid chromatography-electrical chemical detection （HPLC-ECD）. The results showed that pretreatment with genistein or estrogen significantly antagonized MPTP-induced losses of both TH-IR neurons and TH mRNA levels in the SNpc （P 〈0.01）. MPTP significantly decreased the levels of dopamine （DA） and its metabolites DOPAC and HVA in the Str, which could be restored by genistein or estrogen pretreatment. These findings provide evidence for that genistein has neuroprotective effects on dopaminergic neurons against MPTP-induced neuronal damage in the SN.

关 键 词：PARKINSON病 大豆异黄酮 多巴胺 黑质致密带 纹状体 

分 类 号：R742.5[医药卫生—神经病学与精神病学]