LXR激动剂TO901317抑制N2a/APP695swe细胞内Aβ生成的机制研究  

Mechanism of inhibition of Aβproduction by LXR agonist TO901317 in N2a/APP695swe cells

作　　者：黄杰[1] 张雄[2] 邓煜 陈非 罗英茂[1] 田茗源[3] HUANG Jie;ZHANG Xiong;DENG Yu;CHEN Fei;LUO Yingmao;TIAN Mingyuan(Department of Geratology,Chongqing Mental Health Center,Chongqing 400036,China;School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China;Department of Endocrinology,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆市精神卫生中心老年科,400036 [2]重庆医科大学基础医学院,400016 [3]重庆医科大学附属第二医院内分泌科,400010

出　　处：《重庆医学》2022年第12期1999-2003,共5页Chongqing medicine

基　　金：国家自然科学基金项目(81801389);重庆市自然科学基金项目(Cstc2019jcyj-msxmX0673);重庆医科大学附属第二医院宽仁英才项目(kryc-yq-2214)。

摘　　要：目的观察肝脏X受体(LXR)激动剂TO901317对N2a/APP695swe细胞内β-淀粉样蛋白42(Aβ42)生成的影响,并探索其潜在机制。方法体外培养N2a/APP695swe细胞,并用不同浓度的TO901317(5、10和20μmol/L)作用于细胞,采用ELISA检测细胞上清液中生成的Aβ42水平变化;实时荧光定量PCR(RT-PCR)和Western blot分别检测N2a/APP695swe细胞内淀粉样前体蛋白(APP)、β-分泌酶(BACE1)和小凹蛋白-1(caveolin-1)mRNA和蛋白水平的表达。结果ELSIA结果显示,TO901317明显降低了细胞上清液中生成的Aβ42水平(P<0.01),且呈浓度依赖性。RT-PCR和Western blot结果显示,TO901317明显抑制了APP和BACE1 mRNA及蛋白水平表达(P<0.01),促进了caveolin-1 mRNA和蛋白水平表达(P<0.01)。结论TO901317能明显抑制N2a/APP695swe细胞内Aβ42的生成,其机制可能与TO901317促进caveolin-1的表达,抑制APP和BACE1的表达有关。Objective To observe the effect of liver X receptor(LXR)agonist TO901317 on the production ofβ-amyloid 42(Aβ42)in N2a/APP695swe cells,and to explore its potential mechanism.Methods N2a/APP695swe cells were cultured in vitro and treated with different concentrations(5,10,and 20μmol/L)of TO901317.ELISA was used to detect the level of Aβ42 in the cell supernatant.The mRNA and protein levels of amyloid precursor protein(APP),β-secretase(BACE1)and caveolin-1 in the N2a/APP695swe cells were detected by real-time fluorescent quantitative PCR(RT-PCR)and Western blot,respectively.Results ELISA results showed that TO901317 significantly decreased the level of Aβ42 in the cell supernatant(P<0.01),and it was in a concentration-dependent manner.RT-PCR and Western blot results showed that TO901317 significantly inhibited the expression of APP and BACE1 mRNA and protein(P<0.01),while promoted the expression of caveolin-1 mRNA and protein(P<0.01).Conclusion TO901317 can significantly inhibit the production of Aβ42 in N2a/APP695swe cells,and its mechanism may be related to the fact that TO901317 promotes the expression of caveolin-1 and inhibits the expression of APP and BACE1.

关 键 词：阿尔茨海默病 肝脏X受体 TO901317 Β淀粉样蛋白 小凹蛋白-1 神经瘤母细胞 

分 类 号：R749.16[医药卫生—神经病学与精神病学]