基于网络药理学探究桃仁–红花调控动脉粥样硬化斑块稳定性的潜在机制

Exploring the Potential Mechanism of Peach Kernel-Safflower in Regulating the Stability of Atherosclerotic Plaque Based on Network Pharmacology

目的:探究桃仁–红花调控动脉粥样硬化斑块稳定性的潜在机制。方法:对GEO数据库中的动脉斑块相关数据集进行差异分析,得到动脉粥样硬化斑块稳定性相关基因。从TCMSP数据库获取桃仁–红花的有效成分和潜在靶点。对两者取交集后找出发挥作用的化合成分和潜在靶点。对潜在靶点进行PPI、GO、KEGG分析,探究桃仁–红花调控动脉粥样硬化斑块稳定性的作用机制。结果:对稳定斑块组和破裂斑块组差异分析后,共找出1577个差异基因。通过TCMSP共找出桃仁–红花中的16个化学成分,193个靶点。两者取交集后得到28个桃仁–红花调控动脉粥样硬化斑块稳定性的潜在靶点。PPI结果显示,MMP2、CCND1、CXCL8、CAV1、HMOX1、AR、VCAM1、PGR、ABCG2等28个交集基因之间有较强的相互作用关系。且DPP4、HMOX1、Cav-1和VCAM-1处于PPI网络的枢纽位置。GO结果表明,BP与对抗生素的反应、腺体发育、对营养物质的反应有关。CC与膜筏、膜微域、膜区等细胞区域有关。MF与核受体活性、配体激活的转录因子活性、甾体荷尔蒙受体活性有关。KEGG结果与流体剪切应力与动脉粥样硬化、脂肪细胞中脂肪分解的调节、雌激素信号传导途径、内分泌抵抗、NF-kappa B信号传导途径、脂质和动脉硬化、血小板激活传导有关。结论:桃仁–红花内的药物成分可能通过调节MMP2、CCND1、CXCL8、CAV1、HMOX1、AR、VCAM1等靶点影响相关信号传导途径,进而干预斑块稳定性。

Objective: To explore the potential mechanism of peach kernel-safflower regulating the stability of atherosclerotic plaque. Methods: The genes related to the stability of atherosclerotic plaques were obtained by differential analysis of the arterial place-related data sets in the GEO database. The effective components and potential targets of peach kernel-safflower were obtained from the TCMSP database. After the intersection of the two compounds, the active compounds and potential targets were found. PPI, GO and KEGG analyses were performed on potential targets to explore the mechanism of peach kernel-safflower regulating the stability of atherosclerotic plaque. Results: A total of 1577 differential genes were identified by the difference analysis between the stable plaque group and the ruptured plaque group. A total of 16 chemical components and 193 targets in peach kernel-safflower were identified by TCMSP. Twenty-eight potential targets of peach kernel-safflower regulating the stability of atherosclerotic plaque were obtained by the intersection of the two. PPI results showed that there were strong interactions among 28 intergenes, such as MMP2, CCND1, CXCL8, CAV1, HMOX1, AR, VCAM1, PGR, ABCG2 and so on. DPP4, HMOX1, Cav-1 and VCAM-1 are at the hub of the PPI network. GO results showed that BP was related to the response to antibiotics, glandular development and the response to nutrients. CC is related to membrane raft, membrane microdomain, membrane region and other cellular regions. MF was related to nuclear receptor activity, ligand-activated transcription factor activity and steroid hormone receptor activity. KEGG results were related to fluid shear stress and atherosclerosis, regulation of lipolysis in adipocytes, estrogen signaling pathway, endocrine resistance, NF-kappa B signaling pathway, lipid and arteriosclerosis and platelet activation pathway. Conclusions: The drug components in peach kernel-safflower may affect the signal transduction pathway by regulating MMP2, CCND1, CXCL8, CAV1, HMOX1, AR, VCAM1 and other targets, so as to interfere with plaque stability.