基于网络药理学分析丹参山楂组分配伍抗动脉粥样硬化的作用机制研究

Explore anti-atherosclerotic mechanism of component compatibility of Danshen and Shanzha based on network pharmacology and cell level

该文基于网络药理学预测及体外细胞验证的方法,对丹参山楂有效组分配伍(SC121)抗动脉粥样硬化(AS)的作用机制进行了探讨。根据SC121所含成分的结构类型及药效活性报道,选取丹酚酸B、丹参酮ⅡA、丹参素、表儿茶素及原花青素B2作为SC121的主要活性成分,用于网络药理学分析。运用TCMSP数据库,筛选上述5个主要成分作用于心血管疾病的网络靶点;结合KEGG和Uniprot数据库,进行信号通路和生物途径分析,预测其作用机制。在网络药理学预测的基础上,建立体外细胞模型,观察SC121对ox-LDL诱导人脐静脉内皮细胞(HUVEC)和巨噬细胞RAW264.7损伤及泡沫化的保护作用。网络分析结果显示,SC121可通过作用同一靶点或不同靶点发挥抗AS作用,其作用机制与调节PPAR,renin-angiotensin system等多通路,参与炎症反应、内皮细胞保护及脂质生物合成和代谢等多生物途径有关。细胞实验结果表明,SC121可减轻ox-LDL对HUVEC和RAW264.7的损伤程度,降低RAW264.7细胞内活性氧水平,减少泡沫细胞面积,并呈一定的量效关系。即在体外细胞模型上,SC121可抑制内皮细胞损伤、抗氧化等,验证了网络药理学的预测结果,综合阐释了SC121抗AS的作用机制。

To explore the anti-atherosclerotic mechanism of active component compatibility of Danshen and Shanzha（ SC121） based on network pharmacology and in vitro research validation with cell model. On one hand,according to the chemical structures and pharmacological activities of the compounds reported in Danshen and Shanzha,5 compounds,i. e.,salvianolic acid B,tanshinone ⅡA,tanshinol,epicatechin and procyanidin B2 were chosen and used for network pharmacology analysis. Then the TCMSP（ http：//lsp. nwsuaf. edu. cn/tcmsp. php） was used for finding the network targets for 5 compounds from SC121. The signaling pathway associated with cardiovascular disease was analyzed by KEGG mapping,the biological process associated with cardiovascular disease was analyzed by Uniprot. And,the mechanism of SC121 was predicted by network pharmacology. In vitro cell model was subsequently performed for validation. HUVEC and RAW264. 7 cell injuries and foam cell formation were constructed by ox-LDL,and the intervention effects of SC121 were assayed. The result showed that SC121 not only alleviated the damage of HUVEC and RAW264. 7,lowered the ROS level,but also decreased the area of foam cell in a dose-dependent manner,which indicated that SC121 could inhibit the damage of endothelial cells and lower the oxidative stress. The experimental data validated the prediction of network pharmacology,and elucidated the mechanism of SC121’s effect on AS.