淫羊藿素对β淀粉样蛋白生成相关途径的影响  

Effect of icaritin onβ-amyloid production-related pathways

作　　者：冯飞 李莹 黄南渠 李园园 罗勇 FENG Fei;LI Ying;HUANG Nanqu;LI Yuanyuan;LUO Yong(Department of Neurology,the Third Affiliated Hospital of Zunyi Medical University/Zunyi First People′s Hospital,Zunyi,Guizhou 563000,China;Department of Neurology,Guiyang First People′s Hospital,Guiyang,Guizhou 550000,China;GCP Office,the Third Affiliated Hospital of Zunyi Medical University/Zunyi First People′s Hospital,Zunyi,Guizhou 563000,China)

机构地区：[1]遵义医科大学第三附属医院/遵义市第一人民医院神经内科,563000 [2]贵州省贵阳市第一人民医院神经内科,550000 [3]遵义医科大学第三附属医院/遵义市第一人民医院GCP办公室,563000

出　　处：《重庆医学》2020年第11期1721-1725,共5页Chongqing medicine

基　　金：国家自然科学基金项目(81860710,81650030);贵州省科技厅项目(黔科合基础[2016]1165);遵义市科技基金项目(科合社字[2018]160号);贵州省中医药管理局项目(QZYY-2016-018,QZYY-2018-098)。

摘　　要：目的探讨淫羊藿素(ICT)对β淀粉样蛋白(Aβ)生成相关途径的作用机制。方法将具有过表达β位淀粉样前体蛋白裂解酶1(BACE1)质粒的脂质体转染至APP-PS1-HEK293细胞,分为对照组(不添加药物的等体积溶媒)、ICT低剂量组(0.5μmol/L)、ICT中剂量组(5.0μmol/L)、ICT高剂量组(10.0μmol/L)。应用Western blot、ELISA、定量PCR等方法检测ICT对Aβ生成相关途径中Aβ1-40、BACE1、早老素1(PS1)、解整合素金属蛋白酶10(ADAM10)的影响。结果ICT低、中、高剂量组Aβ1-40的表达水平分别为(122.110±10.900)、(95.860±5.309)、(79.610±4.739)pg/mL,较对照组的(134.330±5.221)pg/mL明显降低(P<0.05);BACE1 mRNA表达水平分别为2.140±0.042、1.510±0.081和1.170±0.061,较对照组(3.300±0.036)明显降低(P<0.05);PS1 mRNA表达水平分别为1.570±0.080、1.370±0.078和1.070±0.065,较对照组(2.140±0.044)明显降低(P<0.05);ADAM10 mRNA表达水平分别为0.840±0.079、1.150±0.026和1.520±0.080,较对照组(0.580±0.033)明显升高(P<0.05)。ICT中、高剂量组BACE1、PS1和ADAM10蛋白表达水平和对照组相比,差异均有统计学意义(P<0.05)。结论ICT可通过下调BACE1和PS1表达水平,上调ADAM10的表达水平,从而参与抑制Aβ的生成。Objective To explore the action mechanism of icaritin(ICT)onβ-amyloid(Aβ)production-related pathways.Methods Liposomes with overexpressed amyloid precursor protein lyase 1(BACE1)plasmid were transfected into APP-PS1-HEK293 cells,which were divided into the control group(iso-volume solvent without added drugs),the ICT low-dose group(0.5μmol/L),the ICT medium-dose group(5.0μmol/L),and the ICT high-dose group(10.0μmol/L).Western blot,ELISA and quantitative PCR were used to detect the effect of ICT on Aβ1-40,BACE1,presenilin 1(PS1)and integrin metalloproteinase 10(ADAM10).Results The content of Aβ1-40 was(122.110±10.900),(95.860±5.309)and(79.610±4.739)pg/mL in the ICT low-dose,mediam-dose,and the high-dose group,respectively,which were significantly lower than that of the control group[(134.33±5.221)pg/mL,P<0.05],respectively.The mRNA expression of BACE1 was 2.140±0.042,1.510±0.081 and 1.170±0.061 in the ICT low-dose,mediam-dose,and the high-dose group,which were significantly decreased when compared with the control group(3.300±0.036,P<0.05),while the mRNA expression leve of PS1 was 1.570±0.080,1.370±0.078 and 1.070±0.065,respectively,which were also reduced when compared with the control group(2.140±0.044,P<0.05).The ADAM10 mRNA expression was 0.840±0.079,1.150±0.026 and 1.520±0.080 in the ICT low-dose,mediam-dose,and the high-dose group,respectively,which were increased when compared with the control group 0.580±0.033,P<0.05.Compared with the control group,the protein expression levels of BACE1,PS1 and ADAM in the medium-dose and the high-dose group were significantly different(P<0.05).Conclusion ICT can down-regulate the expression of BACE1,PS1 and up-regulate the expression of ADAM10,and takes part in regulating the pathway of Aβproduction.

关 键 词：淫羊藿素 淀粉样Β蛋白前体 淀粉样β肽类 阿尔茨海默病 

分 类 号：R96[医药卫生—药理学]