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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 investigate the effects of long-term low-dose hormone replacement therapy (HRT) on plasma sex hormone levels, hippocampal volume and cognitive function in postmenopausal women with Alzheimer’s disease (AD) risk apoE ε4 genotype. Methods Female workers in Peking Union Medical College Hospital from the age of 50 to 87 years were screened and divided into HRT group (n = 83) and control group (n = 99). DNA was extracted from samples and polymerase chain reaction (PCR) - restriction endonuclease polymorphism The plasma apoE genotypes were determined by RFLP. The levels of plasma estradiol (E2), progesterone (P) and testosterone (T) were measured by enzyme-linked immunosorbent assay. The percentage of whole brain volume was calculated by using CVLT, LM, FC, VF, DS, and DS of the University of California at UCLA A total of six methods for the total score (LSMEAN). Results There was no difference in apoE genotype and allele distribution between HRT group and control group. The level of E2 in the carriers of ε4 gene (pmol / L) was significantly higher in the HRT group (n = 14, 79.48 ± 21.55) than in the control group (n = 11, 37.04 ± 7.96, P < difference. LSMEAN had no significant difference between the two groups; however, the volume of the hippocampus (sum of left and right and both sides) in the whole brain volume ratio in HRT group (0.406 ± 0.028) was significantly higher than that in control group (0.369 ± 0.031) (P <0.01). Conclusion HRT can obviously inhibit the atrophy of hippocampus in carriers of ApoEε4 gene, suggesting that long-term, low-dose HRT may be of great importance in the prevention of AD in women with ε4.