目的 利用網(wǎng)絡(luò)藥理學(xué)的方法探究瓜蔞皮注射液治療冠心病穩(wěn)定型心絞痛的網(wǎng)絡(luò)調(diào)控機制。方法 以方中主要成分兼顧主要結(jié)構(gòu)類型為選取原則，確定了瓜蔞皮注射液19個化合物為研究對象，通過Swiss Target Prediction、TCMSP數(shù)據(jù)庫預(yù)測化合物潛在作用靶點，通過GeneCards、DisGeNET、OMIM數(shù)據(jù)庫收集冠心病及穩(wěn)定型心絞痛的疾病靶點，將藥物靶點和疾病靶點取交集，利用Cytoscape軟件構(gòu)建“成分–靶點”網(wǎng)絡(luò)。采用String數(shù)據(jù)庫構(gòu)建蛋白互作網(wǎng)絡(luò)，借助Omicsbean軟件及KEGG數(shù)據(jù)庫進行基因本體（gene ontology，GO）功能富集分析及信號通路分析。通過過氧化氫（H₂O₂）誘導(dǎo)的H9c2心肌細胞氧化應(yīng)激損傷模型，對關(guān)鍵成分進行活性驗證。結(jié)果 篩選出19個化合物的110個疾病靶點，經(jīng)分析網(wǎng)絡(luò)拓撲參數(shù)獲得14個關(guān)鍵靶點：GAPDH、TNF、EGFR、MMP9、PTGS2、ACHE、REN、PPARG、F2、HSP90AA1、MMP2、IL2、HMOX1、FGF2，通過參與調(diào)節(jié)PI3K-Akt、血小板活化、腎素血管緊張素系統(tǒng)、細胞凋亡、腫瘤壞死因子、花生四烯酸代謝、鈣離子等信號通路來發(fā)揮治療冠心病及穩(wěn)定型心絞痛的作用。結(jié)論 瓜蔞皮注射液主要通過抗炎、保護血管內(nèi)皮、調(diào)節(jié)氧化應(yīng)激、干預(yù)腎素血管緊張素系統(tǒng)、調(diào)節(jié)能量代謝等途徑發(fā)揮對冠心病及穩(wěn)定型心絞痛的治療作用。

Objective Explored the network regulation mechanism of Gualoupi Injection for the treatment of coronary heart disease and stable angina pectoris using network pharmacology. Methods Based on the selection principle of main components and main structural types, 19 compounds of Gualoupi Injection were determined as the research object. The potential targets of compounds were predicted through Swiss Target Prediction and TCMSP databases. The disease targets of coronary heart disease and stable angina pectoris were collected through GeneCards, DisGeNET, and OMIM databases. The drug targets and disease targets were intersected, and the "component- target" network was constructed by Cytoscape software. The protein-protein interaction network was constructed using string database, and the gene ontology (GO) function enrichment analysis and signal pathway analysis were carried out with the help of Omicsbean software and KEGG database. The activity of key components was verified by the H₂O₂-induced H9c2 cells injury model. Results 110 Disease targets of 19 compounds were screened, and 14 key targets including APDH, TNF, EGFR, MMP9, PTGS2, ACHE, REN, PPARG, F2, HSP90AA1, MMP2, IL-2, HMOX1, and FGF2 were obtained by analyzing the network topology parameters, which play a role in the treatment of coronary heart disease and stable angina pectoris by participating in the regulation of PI3K-Akt signaling pathway, platelet activation, renin-angiotensin system, apoptosis, TNF signaling pathway, and arachidonic acid metabolism, calcium signaling pathway and other signaling pathways. Conclusion Gualoupi Injection plays a therapeutic role on coronary heart disease and stable angina pectoris mainly through anti-inflammatory, protecting vascular endothelium, regulating oxidative stress, intervening renin angiotensin system and regulating energy metabolism.

R285

天津市科技計劃項目（20KPHDRC00020）