雌激素对帕金森病大鼠中脑黑质多巴胺能神经元的保护作用

背景雌激素对中脑黑质多巴胺含量的影响在国内外已有报?雌激素的神经细胞保护作用还正处于研究中.目的观察雌激素对去卵巢大鼠中脑黑质多巴胺能神经元的作用,探讨雌激素对帕金森病防治的可能性.设计以实验动物为研究对象,随机对照的验证性研究.单位一所军医大学医院的全军神经外科研究所.材料实验于2003-10/2004-02在解放军第四军医大学西京医院全军神经外科研究所进行试验,选择一级健康雌性Wistar大鼠50只.干预50只大鼠随机分为5组,第1组为正常对照组,第2组为假手术组,第3,,5组为去卵巢组第3组术后给予10μg(2次/d)的苯甲酸雌二醇,第4组给予雌激素的同时给予雌激素受体拮抗剂三苯氧胺5μg(2次/d).第5组不给药物.每组10只.应用立体定向技术注射6-羟基多巴胺于大鼠中脑黑质,采用免疫组织化学的方法对黑质TH阳性神经元进行标记、记数.同时,对大鼠的行为学进行观测.主要观察指标①各组大鼠在阿朴吗啡诱导下的旋转圈数.②各组大鼠手术后30 d中脑黑质TH阳性神经元数量.结果正常对照组、假手术组与应用雌激素各组之间差异无显著性意义(P＞0.05).手术后苯甲酸雌二醇组与无药组之间差异有显著性意义(P＜0.05).应用雌激素同时应用三苯氧胺组与苯甲酸雌二醇组差异有显著性意义(P＜0.05);与无药组之间差异也存在显著性意义(P＜0.05).大鼠中脑黑质TH阳性神经元数目与其他对照组比较也有显著性意义(P＜0.05).结论雌激素对雌性大鼠中脑黑质多巴胺能神经元具有保护作用,除了经过雌激素受体途径以外,还有其他的作用机制.

Neuroprotective effects of estrogen on nigral dopaminergic neurons in the midbrains of rats with Parkinson disease

BACKGROUND: There have been reports at home and abroad about effects of estrogen upon the dopamine amount in substantia nigra in the midbrains while the neuroprotective effects of estrogen are still being studied.OBJECTIVE: To observe the effects of estrogen on dopaminergic neurons and explore the feasibility of preventing and treating Parkinson disease with estrogen.DESIGN: A randomized controlled study based on the experimental animals.SETTING: General neurosurgery institute in a hospital of a military medical university of Chinese PLA.MATERIALS: The trial was conducted in the General Neurosurgery Institute of Xijing Hospital,the Fourth Military Medical University of Chinese PLA from October 2003 to February 2004 with 50 healthy,first-grade Wistar rats as subjects. INTERVENTIONS: The rats were randomly assigned into 5 groups with 10in each group. Group 1 was normal control,group 2 sham-operation group,and groups 3,4,5 were ovariectomy groups. In group 3,10 μg of estradiol was administered twice a day ineach rat after ovariectomy. Each rat in group 4 was administered with estrogen antagonist,5 μg tamoxifen twice a day as well as estrogen. In group 5,only ovariectomy was performed. After stereotaxic injection of 6-hydroxydopamin into substantia nigra in the midbrains,the TH positive neurons were labeled and counted with immunohistochemic method and the rat's behavior was observed.MIAN OUTCOME MEASURES:①the circles of rat's rotation provoked by apomorphine.②the TH positive neuron count in the middrains of rat's substantia nigra 30 days after ovariectomy.RESULTS: Baseline characteristics among the groups were no difference ( P ＞ 0.05). The result of group 3 was different from that of group 5 ( P＜ 0.05 ). The result of group 4 was also different from that of group 3 and group 5 (P ＜ 0.05) . The TH positive neuron count in the midbrains ingroup 3 also differed from that in other groups( P ＜ 0.05).CONCLUSION: Estrogen acts as a neuroprotectant of the nigral dopaminergic neurons in the midbrains not only through estrogen receptor-dependent pathways but probably also through others.