TO901317对海马神经元β-分泌酶表达及β-淀粉样肽生成的影响  

The effect of TO901317 on the expression of β-secretase and β-amyloid peptide in hippocampal neuron

作　　者：张淑坤[1] 姜玲玲[1] 刘洁[1] 杨荣慧[2] 侯艳宁[2] 

机构地区：[1]河北医科大学生物化学与分子生物学教研室,河北石家庄050017 [2]白求恩国际和平医院

出　　处：《中国老年学杂志》2007年第20期1953-1955,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(30371566);河北省自然科学基金(303472)

摘　　要：目的研究肝X受体(LXR)配体TO901317对海马神经元淀粉样前体蛋白(APP)、α-分泌酶(ADAM10)和β-分泌酶(BACE1)mRNA表达的影响及与β-淀粉样肽(Aβ)生成的关系。方法大鼠海马神经元培养至第7天,在饲养液中加入2.0μmol/LTO901317,继续培养48h。应用RT-PCR方法研究海马神经元APP、ADAM10和BACE1等基因的mRNA的表达,放免法检测培养液Aβ含量的变化。结果TO901317降低海马神经元APP和BACE1 mRNA表达(P<0.01),减少培养液Aβ含量(P<0.01),但不影响ADAM10 mRNA表达(P>0.05)。结论TO901317激活LXR,能通过降低APP和BACE1的表达来减少海马神经元Aβ分泌。Objective To investigate the effects of liver X receptor（LXR） ligand TO901317-LXR on the expression of β-amyloid precursor protein （APP） ,α-secretase （ADAM10） and β-secretase （ BACE1 ） in hippocampal neuron. Methods On the 7 th day ,hippocampal neurons were treated with 2.0 μmol/L TO901317. The expression of APP,ADAM10 and BACE1 mRNA were measured by RT-PCR and the content of Aβ in culture fluid was measured by radioimmunoassay method after cultured 48 h. Results TO901317 decreased the expression of APP and BACE1 mRNA （P 〈 0. 01 ） and the content of Aβ（ P 〈 0, 01 ）significantly, but had no effect on the expression of ADAM10 mRNA （ P 〉 0. 05 ）. Conclusions TO901317 could activate LXR and decrease the secretion of Aβ by decreasing the expression of APP and BACE1 mRNA in hippocampal neuron.

关 键 词：肝X受体 TO901317 β-淀粉样肽前体蛋白 Β-分泌酶 Β-淀粉样肽 

分 类 号：R749.1[医药卫生—神经病学与精神病学]