绝经后妇女长期低剂量激素替代疗法的研究——II.对apoEε4基因携带者海马的保护作用  

The study on long-term low dose sex-hormone replacement therapy in postmenopausal women—II.The protection of hippocampus in apoE ε4 carriers

作　　者：岳赟[1] 左萍萍[1] 胡凌[2] 董毅龙[1] 洪霞[2] 葛秦生[2] 

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院药理室,北京100005 [2]北京协和医学院北京协和医院,北京100730

出　　处：《生殖医学杂志》2008年第4期241-245,共5页Journal of Reproductive Medicine

基　　金：科技部1999年度攀登-特别支持费资助项目(国科基字[1999]045)

摘　　要：目的观察阿尔兹海默病（AD）危险因子apoEε4基因型绝经后妇女长期低剂量激素替代疗法（HRT）对血浆性激素水平、脑海马体积和认知功能的影响。方法筛选50-87岁北京协和医院女职工，分为HRT组（83例）和对照组（99例），提取样本DNA后，采用聚合酶联反应（PCR）-限制性内切酶多型性（RFLP）法测定apoE基因型；酶联免疫法测血浆雌二醇（E2）、孕激素（P）和睾酮（T）水平；磁共振成像（MRI）技术，比较两组间脑海马体积占全脑容量百分比；采用WHO-加利福尼亚大学（UCLA）词语学习（CVLT）、逻辑记忆（LM）、复杂图形（FC）、词语流畅性（VF）、结构实例（CP）、数字广度（DS）评定方法共六项之和为认知总分（LSMEAN）。结果HRT组与对照组apoE基因型和等位基因分布无差异。ε4基因携带者E2水平（pmol/L）HRT组[14例，（79.48±21.55）]明显高于对照组[11例，（37.04±7.96）]（P〈0.05）；P和T未见明显差异。LSMEAN在两组间无显著差异；但海马（左、右及两侧之和）体积占全脑体积之比HRT组（0.406±0.028）明显大于对照组（0.369±0.031）（P〈0.01）。结论HRT可明显抑制ApoEε4基因携带者海马的萎缩，提示长期小剂量HRT对携带ε4绝经后妇女预防AD具有重要意义。Objective： To study the effects of long-term low dose sex-hormone replacement therapy（HRT） on sex hormone,the volume of hippocampus and cognitive function in the postmenopausal women carrying apoE ε4,predisposing gene of Alzheimer＇s disease（AD）.Method： Participants were selected from the postmenopausal women staff of Peking Union Medical College Hospital who aged 50-87 years,with 83 women in HRT group and 99 in control group.Genomic DNA was isolated from blood cells and ApoE genotyping was performed by PCR-RFLP.Plasma levels of estradiol（E2）,progesterone（P） and testosterone（T） were assayed by enzyme linked immunosorbent assay（ELISA）.Magnetic resonance imaging（MRI） was performed to determine the volume of brain hippocampus.Cognitive ability was assessed by California verbal learning test（CVLT）,logical memory （LM）,figure complex（FC）,verbal fluency（VF）,constructional praxis（CP） and digit span（DS）.The sum of these scores was used to evaluate the overall cognitive ability and manifested by LSMEAN.Results： The distribution of apoE alleles and frequency in the both HRT and control groups were shown no significant difference.Plasma E2 concentration in apoE ε4 carriers in the HRT group（14 subjects） was significantly higher than that in the control group（11 subjects）（P〈0.05）.No significant difference was observed in plasma P,T concentration and the LSMEAN between two groups.Further analysis with the apoE ε4 carriers showed that both left and right hippocampus volumes of control group were significantly smaller than those of HRT group.Conclusion： This study showed that HRT attenuated the atrophy of hippocampus in apoE ε4 carriers,suggesting that long-term low dose HRT might be beneficial to reduce the risk of AD development in vulnerable postmenopausal women.

关 键 词：ApoEε4基因 HRT 绝经后妇女 海马 磁共振成像 

分 类 号：R711.75[医药卫生—妇产科学]