长期口服雌激素对去卵巢大鼠海马结构内β-淀粉样前体蛋白及其mRNA表达的影响  

Effects of long-term replacement therapy estrogen on the expression of beta-amyloid precursor protein and mRNA in OVX rat hippocampal formation

作　　者：蒋波[1] 廖二元[2] 谭利明[1] 戴如春[2] 肖志杰[1] 

机构地区：[1]中南大学湘雅二医院神经内科,湖南长沙410011 [2]中南大学湘雅二医院代谢内分泌研究所

出　　处：《中国老年学杂志》2006年第11期1491-1494,共4页Chinese Journal of Gerontology

基　　金：“十五”国家医学科技攻关课题（2001BA702B03）

摘　　要：目的观察长期口服复方尼尔雌醇和小剂量17β-雌二醇补充治疗对去卵巢大鼠海马结构内β-淀粉样前体蛋白(β-APP)及其mRNA表达的影响。方法7月龄SD大鼠按体重随机分成5组正常对照组、假手术组(SHAM)、去卵巢组(OVX)、17β-雌二醇预防干预组(OVX/ERT)和复方尼尔雌醇预防干预组(OVX/NL)连续观察。5组均在去卵巢后35w处死。用免疫组织化学方法(SABC法)显示大鼠海马结构内β-APP,原位杂交方法显示β-APPmRNA。细胞计数及图像分析观察β-APP及其mRNA的变化。结果OVX组海马结构内各亚区β-APP阳性神经元数量和平均光密度均高于正常组、SHAM组、OVX/ERT组、OVX/NL组(P<0.05),而β-APPmRNA阳性神经元数量和平均光密度在5组之间均无显著性差异。结论长期雌激素缺乏导致了大鼠海马结构内β-APP含量的增加,长期口服复方尼尔雌醇和小剂量17β-雌二醇补充治疗可减少β-APP的含量,且二者效果相当。促进β-APP分解、减少β-APP的含量,进而减少Aβ的沉着可能是雌激素神经保护的重要机制之一。Objective To investigate the effects of long-term replacement therapy of compound nylestriol tablet or low-dose 17betaestradiol on the expression of beta-amyloid precursor protein （β-APP） and mRNA in OVX rat hippocampal formation. Methods Fifty seven- month-old female Sprague-Dawley rats were randomly divided into five groups： normal control, SHAM, OVX, OVX plus 17beta-estradiol （OVX/ERT） ,and OVX plus compound nylestriol tablet （OVX/NL）. Immunohistochemistry of β-APP was used to determine the levels of β- APP expression in OVX rathippocampal formation and the expression of β-APP mRNA was documented using in situ hybridization. The results were quantitatively analyzed using cell counting and imaging system. Results A dramatic increase in number and optical density of β-APP- positive neurons in OVX rat hippocampal formation was found （ P 〈 0. 05 ） though there was no difference in number and optical density of β- APP mRNA-positive neurons among normal control, SHAM, OVX/NL and OVX/ERT rats. Conclusions The long-term estrogen deficiency results in an increase of expression of β-APP though no changes in the expression of β-APPmRNA detected. Replacement of low-dose 17betaestradiol or compound nylestriol tablet can equally inhibit the expression of β-APP in hippocampal formation,which may be the main mecha- nism of estrogen＇s neuroprotective effect.

关 键 词：去卵巢大鼠 复方尼尔雌醇 17Β-雌二醇 海马结构 Β-淀粉样前体蛋白 

分 类 号：R711.75[医药卫生—妇产科学]