目的 應(yīng)用網(wǎng)絡(luò)藥理學(xué)與分子對接的方法闡明異鉤藤堿抗肺纖維化的作用機制。方法 使用Swiss Target Prediction、DisGeNET等數(shù)據(jù)庫預(yù)測異鉤藤堿和肺纖維化的潛在靶點。通過拓撲分析篩選核心靶點，并對其進行基因本體論（GO）功能和京都基因和基因組百科全書（KEGG）通路富集分析。對篩選出的關(guān)鍵靶點進行分子對接實驗驗證結(jié)合活性。結(jié)果 靶點預(yù)測得到100個異鉤藤堿和肺纖維化共同作用靶點，GO功能分析表明調(diào)節(jié)炎癥反應(yīng)、正向調(diào)節(jié)成纖維細胞增殖等多種生物過程參與肺損傷后的纖維化進程；得到了MAPK1、MAPK3、EGFR、VEGFA、PI3KCA、PI3KCD、AKT1、TNF等8個異鉤藤堿治療肺纖維化的預(yù)測靶點和以PI3K-Akt信號通路為主的潛在作用途徑。分子對接結(jié)果表明異鉤藤堿可以與選定的8個靶點進行結(jié)合。結(jié)論 異鉤藤堿可以通過調(diào)節(jié)肺纖維化的某些生物過程，介導(dǎo)以PI3K-Akt信號通路為主的途徑發(fā)揮肺損傷后的保護作用，為后續(xù)開展異鉤藤堿抗肺纖維化的實驗研究提供理論依據(jù)。

Objective Application of network pharmacology and molecular docking to elucidate the mechanism of isorhynchophylline against pulmonary fibrosis. Methods The potential targets of isorhynchophylline and pulmonary fibrosis were first predicted through Swiss Target Prediction, DisGeNET, and other databases. Then the core targets were screened by topological analysis and subjected to Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, molecular docking was performed to verify the binding activity. Results Target prediction yielded 100 predicted targets where isorhynchophylline and pulmonary fibrosis act together, and GO functional analysis indicated that multiple biological processes such as regulation of inflammatory response and positive regulation of fibroblast proliferation are involved in the fibrosis process after lung injury. Ultimately, MAPK1, MAPK3, EGFR, VEGFA, PI3KCA, PI3KCD, AKT1, TNF eight predicted targets of isorhynchophylline for the treatment of pulmonary fibrosis and a potential pathway based on the PI3K-Akt signaling pathway were identified. In addition, molecular docking results showed that isorhynchophylline could bind to the selected eight targets. Conclusion Isorhynchophylline may exert protective effects after lung injury by modulating certain biological processes of lung fibrosis and mediating a pathway dominated by the PI3K-Akt signaling pathway, providing a theoretical basis for subsequent experiments on the anti-pulmonary fibrosis of isorhynchophylline.

R285.5

國家自然科學(xué)基金資助項目（81160560）；內(nèi)蒙古自然科學(xué)基金項目（2011MS1131，2015MS0809，2019MS08061，2020MS08071，2020MS08077，2021MS08126）；自治區(qū)大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計劃項目（S202119127007）