基于网络药理学探讨黄芩-黄连治疗动脉粥样硬化的作用机制

Exploring the Mechanism of Action of Scutellaria baicalensis-Huanglian in the Treatment of Atherosclerosis Based on Network Pharmacology

摘要: 动脉粥样硬化是一种以脂质代谢紊乱为特征的心脑血管疾病。由于一线药物的不良反应，临床上迫切需要发现新的药物来治疗动脉粥样硬化。黄芩、黄连是中药中最有前景的治疗药物之一。但黄芩、黄连抗动脉粥样硬化的作用机制尚不清晰。在这项研究中，我们使用网络药理学研究黄芩、黄连与动脉粥样硬化之间的相互作用。首先从TCMSP、GEO数据库中确定了与黄芩、黄连的活性成分、潜在靶点和疾病的差异基因。通过两者取交集，确定了14个黄芩、黄连治疗动脉粥样硬化靶点。然后，利用string数据构建了黄芩、黄连和动脉粥样硬化靶点。最后，通过R包进行GO和KEGG功能富集分析。GO分析表明BP涉及脂多糖的反应、对细菌源性分子的反应、细胞对金属离子的反应等过程。CC涉及侧质膜、膜筏等细胞器。MF涉及泛素蛋白连接酶结合、泛素样蛋白连接酶结合等过程。KEGG结果表明，黄芩、黄连治疗AS的信号通路包括IL-17信号传导途径、TNF信号传导途径、脂质和动脉硬化等过程。本研究最后发现，黄芩、黄连改善动脉粥样硬化的作用机制可能是通过影响KCNH2、SCN5A、PTGS2、SLC6A2、ACHE、BCL2L1、MMP9、JUN、THBD、CXCL2、E2F2、ERBB3、FASN、MAPK1等基因的表达进而调控了IL-17、TNF、AGE-RAGE、NF-κB、血管内皮生长因子等信号传导途径实现的。

Abstract: Atherosclerosis is a cardiovascular disease characterised by disturbances in lipid metabolism. Due to the adverse effects of first-line drugs, there is an urgent clinical need to discover new drugs to treat atherosclerosis. Scutellaria baicalensis and Huanglian are among the most promising thera-peutic agents in Chinese medicine. However, the mechanism of action of Scutellaria baicalensis and Huanglian against atherosclerosis is not clear. In this study, we used network pharmacology to in-vestigate the interaction between Scutellaria baicalensis and Huanglian and atherosclerosis. Firstly, differential genes with active ingredients, potential targets and diseases of scutellaria and Huanglian were identified from the TCMSP, GEO database. By taking the intersection of the two, 14 baicalin and scutellaria targets were identified for the treatment of atherosclerosis. Then, baicalin, scutellaria and atherosclerosis targets were constructed using string data. Finally, GO and KEGG were performed by R package for functional enrichment analysis. GO analysis showed that BP in-volved processes such as response to lipopolysaccharide, response to bacterial-derived molecules, and cellular response to metal ions. CC involved organelles such as lateral plasma membrane and membrane rafts. MF involved processes such as ubiquitin protein ligase binding, ubiquitin-like protein ligase binding, and scaffold protein binding. KEGG results indicated that the signalling pathways of Scutellaria baicalensis and Huanglian signaling pathways for the treatment of AS in-clude processes such as IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis. The final finding of this study was that the mechanism of action of Scutellaria baicalensis and Huanglian ameliorating atherosclerosis may be achieved through affecting the expression of genes such as KCNH2, SCN5A, PTGS2, SLC6A2, ACHE, BCL2L1, MMP9, JUN, THBD, CXCL2, E2F2, ERBB3, FASN, MAPK1 and thereby regulating the expression of IL-17, TNF, AGE-RAGE, NF-κB, vascular endothelial growth factor and other signaling pathways.