杨梦琳 周小青 伍大华 张运辉 郑彩杏 童天昊

〔摘要〕 目的 應用网络药理学方法预测何首乌-丹参抗阿尔茨海默病（AD）的作用靶点及相关信号通路，挖掘其抗AD的作用机制。方法 通过中药系统药理学技术平台（TCMSP）网站检索何首乌-丹参的活性成分及对应的作用靶点，再通过Drugbank数据库、Dis Ge NET数据库和TTD数据库获得AD的主要致病靶点，采用Cytoscape 3.7.1软件构建药物活性成分-靶点网络图，利用STRING数据库构建蛋白与蛋白相互作用网络，然后运用生物信息学的方法对关键靶点进行基因功能分析和通路富集分析，最后采用MTT法、ELISA法、比色法和实时荧光定量PCR法对网络药理学主要预测的生物过程与信号通路进行验证。结果 研究共筛选出何首乌-丹参药对的有效成分24个，对应靶点274个，与AD相关靶点共107个，相关信号通路前10条，GO分析相关度前20个靶点分子功能。细胞实验证实了何首乌-丹参能有效提高PC12细胞的细胞存活率及抑制PC12细胞的炎症反应和氧化应激反应，并促进Nrf2/HO-1信号通路的激活。结论 何首乌-丹参主要是通过抗炎和抗氧化应激对AD产生重要的治疗作用，为后续临床治疗AD提供新的思路。

〔关键词〕 何首乌;丹参;阿尔茨海默病;网络药理学;作用机制

〔中图分类号〕R285       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.04.012

〔Abstract〕 Objective To predict he anti-Alzheimer's disease （AD） target and related signaling pathways， and explore the anti-AD mechanism of Heshouwu （Polygoni Multiflori Radix Praeparata）-Danshen （Salviae Miltiorrhizae Radix Et Rhizoma） by network pharmacology. Methods The Chinese medicine system pharmacology technology platform （TCMSP） was used to search the active ingredients and corresponding targets of Heshouwu （Polygoni Multiflori Radix Praeparata）-Danshen （Salviae Miltiorrhizae Radix Et Rhizoma）. The Drugbank database， the Dis Ge NET database and the TTD database were used to obtain the main pathogenic targets of AD. Cytoscape 3.7.1 software was used to construct the active ingredient-target network diagram. STRING database was used to construct the protein-protein interaction （PPI） network. The bioinformatics method was used to analyze the gene function and pathway enrichment analysis of key targets. Finally， the MTT， ELISA， colorimetry method and qRT-PCR were used to verify the main biological processes and signal pathways predicted by network pharmacology. Results A total of 24 active ingredients of Heshouwu （Polygoni Multiflori Radix Praeparata）-Danshen （Salviae Miltiorrhizae Radix Et Rhizoma） were screened ， 274 corresponding targets， 107 targets related to AD， top 10 related signaling pathways， and top 20 target molecular functions by GO analysis. Cell experiments also proved that Heshouwu （Polygoni Multiflori Radix Praeparata）-Danshen （Salviae Miltiorrhizae Radix Et Rhizoma） could effectively improve the cell survival rate of PC12 cells and inhibit inflammation and oxidative stress response of PC12 cells， and promote the activation of Nrf2/HO-1 signaling pathway. Conclusion Heshouwu （Polygoni Multiflori Radix Praeparata）-Danshen （Salviae Miltiorrhizae Radix Et Rhizoma） has an important therapeutic effect on AD mainly through anti-inflammatory and anti-oxidative stress， which provides a new idea for subsequent clinical treatment of AD.

〔Keywords〕 Heshouwu （Polygoni Multiflori Radix Praeparata）; Danshen （Salviae Miltiorrhizae Radix Et Rhizoma）; Alzheimer's

disease; network pharmacology; mechanism of action

阿尔茨海默病（Alzheimers disease， AD）是一种以认知功能下降、精神行為功能障碍为主要表现的神经系统退行性病变[1]。随着全球人口老龄化，AD发病率不断升高，已成为现代医学亟需解决的难题[2]。目前，西医对AD病因及发病机制仍未完全阐明，尚无根治AD的药物[3]。……