激活LXR降低脑Aβ与胆固醇及相关基因转录的关系  

Association of Aβ decreased by activating LXR with cholesterol levels and transcription of cholesterol-related genes

作　　者：石芸[1] 姚敏[1] 侯连国[1] 李静[2] 杨原[1] 姜玲玲[1] 

机构地区：[1]河北医科大学生物化学与分子生物学研究室,石家庄050017 [2]河北省人民医院,石家庄050017

出　　处：《生物学杂志》2013年第3期5-8,共4页Journal of Biology

基　　金：国家自然科学基金(项目编号:30371566);河北省自然科学基金(项目编号:C2011206051)

摘　　要：探讨了激活肝X受体(liver X receptor,LXR)降低的β-淀粉样蛋白(beta-amyloid peptide,Aβ)与脑胆固醇和相关基因转录的关系。给予成年雄性C57BL/6J小鼠口服7 d对照溶剂或LXR的强激动剂TO901317(20mg/kg/d)后,用RT-PCR法检测ATP盒转运体A1(ATP binding cassette transporter A1,ABCA1)和胆固醇-24S-羟化酶(cholesterol-24S-hydroxylase,CYP46)的mRNA表达水平;用氧化酶-比色法测定脑总胆固醇含量;用放免法测定Aβ的含量。结果发现,小鼠口服TO901317后,脑组织中总胆固醇和Aβ的含量降低(P<0.05),LXR的靶基因AB-CA1和非靶基因CYP46的mRNA相对表达量明显增高(P<0.01),脑胆固醇的含量分别与Aβ含量呈正相关(r=0.57,P<0.05),与CYP46 mRNA的相对表达量呈负相关(r=-0.87,P<0.01)。表明激活LXR而降低的Aβ水平与负责胆固醇出胞和胆固醇出脑的相关基因转录增加,脑胆固醇水平降低有关。The association of beta-amyloid peptide （Aβ） decreased by activating liver X receptor （LXR） with cholesterol levels and transcription levels of cholesterol-related genes was studied. Aduh male C57BL/6J mice were administered orally with vehicle solution or LXR agonist TO901317 at 20mg/kg/d for 7 days. The mRNA expression of ATP binding cassette transporter A1 （ ABCA1 ） and cho- lesterol-24S-hydroxylase （CYP46） in brain was detected by RT-PCR. Brain total cholesterol was determined by enzyme oxidation-col- orimetry assay. A~ was determined by radioimmunoassay. The levels of total cholesterol and AI3 were decreased （ P 〈 0.05 ） in the brain of TO901317-treated mice. The mRNA expression of ABCA1 and CYP46 was increased （P 〈0.01 ） in the brain of TO901317- treated mice. Moreover, the cholesterol contents were positively correlated with the A~ levels （r = 0.57, P 〈 0.05 ）and negatively cor- related with CYP46 mRNA levels （ r = - 0.87, P 〈 0.01 ）. Aβ decreased by activating LXR in brain of normal mice is related to de- creased cholesterol levels and increased transcription of genes involved both in cholesterol efflux from cell and in cholesterol elimination from brain.

关 键 词：肝X受体 胆固醇-24S-羟化酶 胆固醇 Β-淀粉样蛋白 

分 类 号：Q78[生物学—分子生物学] R34[医药卫生—基础医学]