蛋白组学联合动力学模拟解析原儿茶酸治疗呼吸道合胞病毒肺炎机制

doi:10.3976/j.issn.1002-4026.2025112

山东科学 ›› 2026, Vol. 39 ›› Issue (5): 21-30.doi: 10.3976/j.issn.1002-4026.2025112

蛋白组学联合动力学模拟解析原儿茶酸治疗呼吸道合胞病毒肺炎机制

孙晓林¹(), 王琳¹, 周芯怡¹, 王成², 张梦茹², 杜海涛²^,^*(), 王平²^,^*()

¹ 山东中医药大学药学院, 山东济南 250355
² 山东省中医药研究院, 山东济南 250014

收稿日期:2025-09-30 修回日期:2026-04-22 出版日期:2026-10-20 上线日期:2026-07-01
通信作者: *杜海涛,男,研究方向为中药抗病毒药理。E-mail: kkitdht@foxmail.com 王平,女,博士,博士研究生导师,研究方向为中药及其活性成分的药效学评价。E-mail:wangpingjinan@126.com
作者简介:孙晓林(1999—),男,硕士,研究方向为临床药学。E-mail: sunxiaolin579@126.com
基金资助:
山东道地药材抗病毒研究科技带头人工作室项目(202228121);山东省中医药科技项目(Q-2023023);山东省技术创新引导计划(中央引导地方科技发展基金)(YDZX2024122);国家中医药管理局科技项目(GZY-KJS-2023-027)

Analysis on the mechanism of protocatechuic acid against RSV pneumonia via proteomics and molecular dynamics simulation

SUN Xiaolin¹(), WANG Lin¹, ZHOU Xinyi¹, WANG Cheng², ZHANG Mengru², DU Haitao²^,^*(), WANG Ping²^,^*()

¹ School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
² Shandong Academy of Chinese Medicine, Jinan 250014, China

Received:2025-09-30 Revised:2026-04-22 Published:2026-10-20 Online:2026-07-01

摘要/Abstract

摘要：

探讨原儿茶酸对呼吸道合胞病毒(RSV)肺炎小鼠的药效作用及其潜在的多靶点作用机制。建立RSV感染的BALB/c小鼠模型,观察小鼠行为学变化,检测肺组织病理损伤、脏器指数及炎症因子水平;蛋白组学方法分析原儿茶酸治疗呼吸道合胞病毒肺炎的差异蛋白,进行GO功能注释、KEGG通路富集及PPI网络分析;运用分子对接和分子动力学模拟验证原儿茶酸与核心靶点的结合稳定性。原儿茶酸能显著改善RSV感染所致小鼠体重下降、肺组织病理损伤及炎症因子过度释放。蛋白组学共鉴定到8 357个蛋白,筛选出142个差异表达蛋白,主要富集于IL-17信号通路、视黄醇代谢和TNF信号通路。分子对接表明原儿茶酸与MAPK8、IGF1等关键靶点具有较强的结合能力,分子动力学模拟进一步提示复合物体系稳定性良好。原儿茶酸可能通过调控IL-17、TNF等相关信号通路,抑制过度炎症反应,从而发挥抗RSV作用,其作用机制涉及多靶点、多通路的协同调控,为中药活性成分抗病毒药物研发提供了理论依据。

关键词: 原儿茶酸, 呼吸道合胞病毒, 蛋白组学, 分子对接, 分子动力学模拟

Abstract:

This study investigates the pharmacological effects of protocatechuic acid on mice with respiratory syncytial virus (RSV) pneumonia and its potential multi-target mechanisms of action. A BALB/c mouse model of RSV infection was established to observe behavioral changes, assess lung tissue pathology, organ indices, and levels of inflammatory cytokines. Proteomics was employed to identify differential proteins involved in the treatment of RSV pneumonia by protocatechuic acid, followed by Gene Ontology functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analysis. Molecular docking and molecular dynamics simulations were conducted to validate the binding stability of protocatechuic acid with core targets. Protocatechuic acid significantly ameliorated RSV-induced weight loss, pulmonary histopathology, and excessive inflammatory cytokine release in mice. A total of 8 357 proteins were identified through proteomics, with 142 proteins differentially expressed and primarily enriched in the interleukin (IL)-17 signaling pathways, retinol metabolism, and the tumor necrosis factor (TNF) signaling pathways. Molecular docking revealed strong binding affinity between protocatechuic acid and key targets such as mitogen-activated protein kinase 8 and insulin-like growth factor 1. Molecular dynamics simulations further indicated robust stability of the complex system. Protocatechuic acid may exert its anti-RSV effects by regulating IL-17- and TNF-related signaling pathways, thereby suppressing excessive inflammatory responses. This mechanism involves synergistic regulation across multiple targets and pathways, providing theoretical support for developing antiviral drugs from active components of traditional Chinese medicine.

Key words: protocatechuic acid, respiratory syncytial virus, proteomics, molecular docking, molecular dynamics simulation

中图分类号:

孙晓林, 王琳, 周芯怡, 王成, 张梦茹, 杜海涛, 王平. 蛋白组学联合动力学模拟解析原儿茶酸治疗呼吸道合胞病毒肺炎机制[J]. 山东科学, 2026, 39(5): 21-30.

SUN Xiaolin, WANG Lin, ZHOU Xinyi, WANG Cheng, ZHANG Mengru, DU Haitao, WANG Ping. Analysis on the mechanism of protocatechuic acid against RSV pneumonia via proteomics and molecular dynamics simulation[J]. Shandong Science, 2026, 39(5): 21-30.

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蛋白组学联合动力学模拟解析原儿茶酸治疗呼吸道合胞病毒肺炎机制

Analysis on the mechanism of protocatechuic acid against RSV pneumonia via proteomics and molecular dynamics simulation

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