脱氢表雄酮对衰老大鼠线粒体外周型苯二氮艹卓受体的影响  

Effects of dehydroepiandrosterone on peripheral benzodiazepine receptors of hippocampus in aged rats

作　　者：陈春富[1] 郎森阳[1] 左萍萍[2] 王湘庆[1] 杨楠[2] 夏程[1] 

机构地区：[1]解放军总医院神经内科,北京100853 [2]中国医学科学院基础医学研究所,北京100005

出　　处：《中国临床药理学与治疗学》2006年第2期187-191,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家重点基础研究计划("973"计划)基金资助项目(№G2000057008)

摘　　要：目的:观察脱氢表雄酮(DHEA)对衰老模型大鼠大脑皮质线粒体外周型苯二氮艹卓受体(PBRs)的影响,探讨PBRs在脑老化中的作用。方法:Sprague-Dawley大鼠随机分为溶媒对照组和药物治疗组。实验动物连续注射D-半乳糖(100 mg.kg-1,qd,共56次)制备衰老动物模型。溶媒对照组、药物治疗组动物分别同时注射二甲基亚砜或DHEA,隔日一次,共28次。利用Morris水迷宫测试学习记忆能力后动物断头,采用梯度离心法制备大脑皮质线粒体,应用放射配基结合试验测定PBRs最大结合容量(Bmax)和平衡解离常数(KD)。结果:与溶媒对照组比较,药物治疗组Bmax显著升高,KD无显著变化,动物学习记忆能力显著改善。大脑皮质线粒体PBRs特异结合活性与迷宫试验动物逃避潜伏期、平台象限游泳距离和时间显著相关(P<0.05)。结论:大脑皮质线粒体PBRs表达量与衰老动物学习记忆功能密切相关。DHEA可以增加脑组织PBRs的表达量,并改善衰老动物智能状态。AIM： To study the effects of dehydroepiandrosterone （DHEA） on peripheral benzodiazepine receptors （PBRs） in cerebral cortex in aged rats as to investigating the role of PBRs in brain aging. METHODS： Sprague-Dawley （SD） rats of both sexes were randomly divided into vehicle control group and DHEA-treated group. All rats received injection of D-galactose （100mg·kg^-1 s. c, once a day for 56 days）. Meanwhile, vehicle- or DHEA-treated rats received dimethyl sulphoxide 1 （ ml·kg^-1 ） or DHEA （30mg·kg^-1, i.p. ） every other day for 28 administrations. Spatial leaming and memory were assessed by Morris water maze test. Following behavioral testing, all rats were decapitated and cerebral cortex was removed immediately. Then, mitochondria were purified by density gradient centrifugation. PBRs binding parameters, maximal binding site density （ Bmax ）and equilibrium dissociation constant （KD）, were estimated by radioligand binding assays. RESULTS： When compared to vehicle controls, DHEA treatment displayed significant elevation of Bmax, without significant changes of KD, and did significant enhancement in learning memory in senescent rats. Specific PBRs binding in cerebral cortex mitochondria was closely related to escaping latencies, swimming time and distance in platform quadrant in Morris water maze in all rats （ P 〈 0.05）. CONCLUSION： Binding density of PBRs in cerebral cortex mitochondria is related to leaming memory performance of aged rats. DHEA can increase the expression of PBRs in brain tissue and improve intellectual status of aged rats.

关 键 词：脑老化 线粒体 脱氢表雄酮 外周型苯二氮[艹卓]受体 学习 记忆 大鼠 

分 类 号：R749[医药卫生—神经病学与精神病学]