雌激素对阿尔茨海默病的干预作用

The effect of estrogen on Alzheimer's disease

目的选择绝经期(65岁前)的轻中度AD(阿尔茨海默病)妇女,给予雌激素替代治疗(HRT),于治疗前、后分别测试其智力的变化;以双侧穹隆-海马伞切断制作AD大鼠模型,并给予雌激素治疗,观察穹隆-海马伞切断组、雌激素治疗组避暗实验的错误次数及潜伏期的变化,及脑内海马区(CA1区)烟碱型乙酰胆碱受体 (nAchR)表达的变化;从临床和基础两方面观察雌激素对AD的干预作用,探讨雌激素的作用及相关机制。方法选择21例绝经期(65岁前)的轻中度AD妇女,随机双盲比较治疗,用老年痴呆认知能力评价表,对治疗前、治疗后 16周分别进行智能评分。健康雌性Wistar大鼠,随机分为穹隆-海马伞切断组和雌激素治疗组;每组大鼠5只。在脑立体定位仪上切断双侧穹隆-海马伞,建立模拟AD的动物模型,对比穹隆-海马伞切断组和雌激素治疗组大鼠的智力变化;并应用免疫组织化学技术观察大鼠脑内CA1区nAchR细胞表达的变化。结果 21例患者行雌激素替代疗法后,修订长谷川量表(HDS-R)及精神认识能力(CCSE)评分比治疗前显著提高(P<0．001,P<0．01),社会活动功能调查(FAQ)评分比治疗前显著降低(P<0．05)。与穹隆-海马伞切断组大鼠比较,雌激素治疗组大鼠避暗实验的错误次数明显减少,潜伏期显著延长(P<0．05),脑内nAchR的表达显著增加(P<0．01)。结论临床和基础实验均证实雌激素能提高AD的智力,并认为其与脑内nAchR表达的增加有关。

Objective To observe the changes of intelligence of AD in menopause （younger than 65） at pretherapy and posttherapy who were given hormone replacement therapy（HRT） and observe the error number of times of avoiding blackness experiment and latent periods and the expression of nAchR in the brain of transection of firnbria/fornix rats and the effect of Ectogenesis Estrogen to the above-mentioned factors and understand the effect on AD. Methods 21 AD patients of menopausal women were treated with diblindness randomly and tested their intelligence at pretheraphy and 16 weeks of posttherapy with senile dementia congnitive ability evaluation meter. Healthy female wistar rats were randomly divided into transection of firnbria/fornix group and estrogen treatment group. There were five rats in every group. And firnbria-fornix of brain was transected in order to make AD model and compared their intelligence with rats were treated with estrogen. Irnrnunoreactive cell of nAchR were stained by irnrnunohistochernical way and observe the expression varieties of nAchR irnrnunoreactive cell in the hippocarnpus CA1. Results The scores of HDS-R and CCSE of AD patients who were treated with HRT were promoted obviously and the scores of FAQ were decreased remarkably. Compared with the transection of firnbria/ fornix group,the error number of times of avoiding darkness were decreased obviously,latent periods were elonged （P〈0.05）and the expression of nAchR distinctively increased in the hippocarnpus CA1 （P〈0.01）in estrogen treatment group. Conclusion Estrogen treatment can promote intelligence and was related to the change of nAchR.