雌激素对去卵巢Parkinson病模型大鼠黑质-纹状体系统多巴胺能神经元的影响

本研究的目的是观察雌激素对多巴胺(DA)能神经元是否具有保护作用。去卵巢(OVX)大鼠分别给予生理盐水(NS)和苯甲酸雌二醇(EB)处理,1周后6OHDA造模,造模2周后灌注取材;利用免疫组化法观察黑质内DA阳性神经元的数量、纹状体中DA能末梢的变化;用TUNEL法观察黑质凋亡细胞的数目并对纹状体中胆碱能神经元进行乙酰胆碱酯酶(AChE)染色,观察其退变情况。结果显示和NS组相比,EB组黑质内DA能神经元数量多、凋亡细胞数少(P<0.05);NS组纹状体内DA能神经元末梢减少60%左右,胆碱能神经元退变明显。结果提示雌激素对DA能神经元具有保护作用,在很大程度上可能与抑制神经元凋亡有关。

EFFECTS OF ESTROGEN ON THE NIGROSTRIATAL SYSTEMATIC DOPAMINERGIC NEURONS IN OVARIECTOMIZED PD MODEL RATS

To determine whether estrogen can provide neuroprotective effects on nigral dopaminergic neurons. The female SD rats were ovariectomized prior to treatment with normal saline (NS) or estradiol benzoate (EB), respectively. One week following the treatment, the Parkinson's disease rat model was developed by unilaterally injecting 6-hydroxydopamine (6-OHDA) into medial forebrain bundle (MFB). Two weeks later, animals from both groups were perfused.The brain slices were processed for TH immunocytochemistry to observe dopaminergic neurons in the substantia nigra (SN) and dopaminergic terminals within the striatum, TUNEL[the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling]method to detect apoptotic dopaminergic neurons and acetylcholinesterase (AChE) histochemistry to reveal the distribution of cholinergic neurons in the striatum, respectively. There were many dopaminergic neurons and few apoptotic neurons in EB group in comparison with those in NS group (P<0.05). Accompanying with the loss of dopaminergic cells in NS group, the content of dopaminergic terminals in the striatum reduced by 60% or so 2 weeks after 6-OHDA insult. Furthermore, the degenerative alterations of the network of cholinergic neurons in NS group were obvious. This experiment showed that estrogen may have neuroprotective effects on dopaminergic cells and the neuroprotection is likely associated with the antiapoptosis.