白藜芦醇通过SIRT1激活ADAM10促进APPα代谢  

Resveratrol promotesα-processing of APP by activating a disintegrin and metalloproteinase 10 via the upregulation of SIRT1

作　　者：黄巍[1] 周曦[1] 周丽荣[1] 卢坤 HUANG Wei;ZHOU Xi;ZHOU Li-rong;LU Kun(Wuhan Institute of Medical Sciences,Wuhan Hubei 430014,China)

机构地区：[1]武汉市卫生健康信息中心(武汉市医学科学研究所),湖北武汉430014

出　　处：《中国医院药学杂志》2022年第6期622-626,共5页Chinese Journal of Hospital Pharmacy

基　　金：武汉市卫计委项目(编号:WX16E20,WX14C71);湖北省自然科学基金(编号:2017CFB174)。

摘　　要：目的:探讨白藜芦醇可否通过SIRT1激活解整合素金属蛋白酶10(ADAM10)促进APPα代谢抑制Aβ分泌。方法:选取过表达人瑞典突变淀粉样前体蛋白APP695sw的细胞模型,分别设立DMSO空白对照组、SIRT1激活剂白藜芦醇组和SIRT1抑制剂EX527组。给药后,ELISA法分别检测细胞培养上清中sAPPα和Aβ的含量,免疫印记Western Blot法检测细胞SIRT1和ADAM10的蛋白水平。结果:与对照组比较,白藜芦醇组细胞培养上清sAPPα的含量增高,Aβ含量下降,sAPPα/Aβ比值增大,细胞SIRT1和ADAM10蛋白水平增高;而抑制剂EX527组与对照相比,细胞培养上清sAPPα的含量降低,Aβ含量升高,sAPPα/Aβ比值减小,细胞SIRT1和ADAM10蛋白水平降低;抑制剂下调SIRT1后各项指标与激动剂组呈现相反的趋势(P<0.05)。结论:白藜芦醇可通过SIRT1激活ADAM10,促进APP进行α非淀粉样代谢途径,增强sAPPα分泌并抑制Aβ产生。OBJECTIVE To investigate whether resveratrol can activate a disintegrin and metalloproteinase 10(ADAM10)to promoteα-processing of APP through SIRT1 metabolic inhibition Aβsecretion.METHODS N2a cells overexpressing Swedish mutation type human APP695(APP695sw/N2a)were divided into DMSO group,RSV group,EX527 group.The concentrations of sAPPαand Aβin conditioned media supernatant were measured by sandwich ELISA.SIRT1 and ADAM10 protein levels were detected by Western Blot.RESULTS Compared with DMSO group,the extracellular level of Aβdecreased while sAPPαincreased in RSV group,sAPPα/Aβratio,SIRT1 and ADAM10 protein levels were increased markedly in RSV group.Compared with DMSO group,the extracellular level of sAPPαdecreased while Aβincreased in EX527 group,sAPPα/Aβratio,SIRT1 and ADAM10 protein levels were decreased markedly in EX527 group(P<0.05).CONCLUSION Resveratrol could promoteα-processing of APP by activating ADAM10 via the upregulation of SIRT1.

关 键 词：白藜芦醇 沉默信息调节因子1 ADAM10 淀粉样前体蛋白 α-代谢 Β淀粉样肽 阿尔茨海默病 

分 类 号：R341[医药卫生—基础医学] R745.7