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目的:探讨雌激素受体(estrogen receptors,ERs)在帕金森病(Parkinson’s disease,PD)中的作用特点。方法:应用经典化学毒素MPTP腹腔注射制备小鼠PD模型,WT、αERKO和βERKO雄性小鼠随机分为Saline组和MPTP组,爬竿试验观察行为学改变,荧光定量PCR法检测纹状体和中脑ERα、ERβ、TH、DAT和VMAT2 mRNA表达的变化。结果:与WT相比,αERKO小鼠中多巴胺缺失程度更大,爬竿试验显示αERKO小鼠更早出现行为学异常。αERKO和βERKO小鼠中脑TH、DAT和VMAT2 mRNA表达均降低。WT小鼠MPTP染毒致PD模型后,纹状体和中脑ERαmRNA表达增加,ERβmRNA表达降低。MPTP致PD模型后,αERKO和βERKO小鼠TH和DAT mRNA表达变化情况与WT小鼠不同,βERKO小鼠VMAT2 mRNA表达变化情况与WT小鼠相同,但αERKO小鼠VMAT2 mRNA表达变化情况与WT小鼠不同。结论:ERs在黑质纹状体DA系统中有神经保护作用,ERα亚型在此过程中发挥着更重要的作用。
Objective: To investigate the role of estrogen receptors (ERs) in Parkinson’s disease (PD). Methods: The mouse model of PD was established by intraperitoneal injection of classical chemical toxins MPTP. The WT, αERKO and βERKO male mice were randomly divided into Saline group and MPTP group. The changes of behavior were observed by climbing rod test. Changes of brain ERα, ERβ, TH, DAT and VMAT2 mRNA expression. Results: Compared with WT, αERKO mice had a greater loss of dopamine, and pole-climbing tests showed earlier behavioral abnormalities in αERKO mice. The mRNA expressions of TH, DAT and VMAT2 in the aERKO and βERKO mice decreased. After PD mouse model induced by MPTP, the expression of ERαmRNA in striatum and midbrain increased and the expression of ERβmRNA decreased. MPTP-induced PD model, αERKO and βERKO mice TH and DAT mRNA expression changes and WT mice, βERKO mice VMAT2 mRNA changes in WT mice the same, but αERKO mouse VMAT2 mRNA expression changes and WT small Different rats. CONCLUSIONS: ERs have neuroprotective effects in the nigrostriatal DA system, and ERα subtypes play a more important role in this process.