阿魏酸治疗阿尔茨海默病的潜在靶点预测及验证  

Prediction and validation of potential targets for Alzheimer′sdisease treatment using ferulic acid

作　　者：陈斯亮 刘梦鸽 史晋宁 徐晓庆 蔡红艳 韩维娜[1] CHEN Siliang;LIU Mengge;SHI Jinning;XU Xiaoqing;CAI Hongyan;HAN Weina(Department of Physiology,Puai Medical College,Shaoyang University,Shaoyang 422000,China;Department of Microbiology and Immunology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]邵阳学院普爱医学院<医学部>生理学教研室,湖南邵阳422000 [2]山西医科大学基础医学院微生物与免疫教研室,山西太原030001

出　　处：《药学研究》2024年第5期428-434,共7页Journal of Pharmaceutical Research

基　　金：国家自然科学基金面上项目(No.82171428);湖南省自然科学基金青年项目(No.2020JJ5517);湖南省教育厅科学研究项目(No.20C1671);国家级大学生创新创业训练项目(No.S202010547043)。

摘　　要：目的利用生物信息学和分子生物学对阿魏酸在阿尔茨海默病(AD)治疗中的靶点进行预测,并研究其在AD中的疗效。方法通过DisGeNET数据库和PubChem数据库获得AD与阿魏酸相互作用的共同基因;DAVID在线数据库对常见靶点进行GO/KEGG富集分析;利用STRING数据库建立蛋白互作网络筛选关键基因;通过免疫印迹和酶联免疫吸附试验,对得到的关键基因的表达进行分析。结果在确定了38个共同作用靶点后,通过蛋白互作网络的构建确定了前3名的基因,分别是基质金属蛋白酶9(MMP9)、Toll样受体4(TLR4)和血管紧张素转化酶(ACE)。在免疫印迹和酶联免疫吸附试验中,阿魏酸下调MMP9、TLR4和ACE的表达(P<0.05)。结论MMP9、TLR4和ACE可作为阿魏酸治疗AD的潜在作用靶点。Objective To predict the potential targets of ferulic acid in the treatment of Alzheimer′s disease(AD)using bioinformatics and molecular biology,and investigat its efficacy in AD.Methods The methodology involved obtaining genes associated with the interaction between AD and ferulic acid from the DisGeNET and PubChem databases,conducting GO/KEGG enrichment analysis of common targets using the DAVID online database,and establishing a protein-protein interaction network to identify key genes through the STRING database;And analyzing the expression of key genes through Western blotting and ELISA.Results After identifying 38 common interaction targets,the construction of a protein-protein interaction network revealed the top three genes,namely MMP9,TLR4,and ACE.In Western blotting and ELISA,ferulic acid was found to downregulate the expression of MMP9,TLR4,and ACE(P<0.05).Conclusion The results suggest that MMP9,TLR4,and ACE may serve as potential therapeutic targets for ferulic acid in the treatment of AD.

关 键 词：阿尔茨海默病 阿魏酸 生物信息学 基质金属蛋白酶9 TOLL样受体4 血管紧张素转化酶 

分 类 号：R285[医药卫生—中药学]