基于网络药理学探讨新型冠状病毒肺炎时方不同治则中药特色机制研究

Study on the Mechanism of Traditional Chinese Medicine with Different Regulations in Corona Virus Disease 2019 Based on Network Pharmacology

目的分析比较新型冠状病毒肺炎(COVID-19)时方中不同治则代表中药的作用机制,以期阐释中药防治新型冠状病毒肺炎不同病程阶段的药理作用机制及主要防治途径。方法依据国家卫生健康委员会发布的《新型冠状病毒感染的肺炎诊疗方案(试行第六版)》中临床治疗期的处方中药,总结疾病证候演变中四类基本治则,并且选定各治则高频次及具有治则代表性的中药构成方药集合,按照治则在SymMap数据库搜索并收集各中药靶标进行分析归纳;用DAVID和STRING软件对各治则靶标分别进行GO生物学过程分析及KEGG信号通路富集分析,总结各治则的主要针对作用通路以及靶点。结果四类治则主要涉及细胞信号转导通路、病毒感染以及多种细胞因子及免疫调控机制。值得注意的是,不同治则方药配伍干预通路侧重点不同,具体表现为散寒胜湿、宣肺解表治则主要作用于恢复机体稳态,调控免疫以防止证候进一步演变;清热化湿、宣肺解毒治则主要作用于抑制病毒体内复制,增强免疫功能等抗病毒途径;清气凉营、解毒清热治则多富集于抑制炎症与细胞分化、抗细胞凋亡途径;复脉固脱、开窍醒神治则多集中于增强机体免疫正向调控为主。结论时方的四类治则从不同角度证明了中医药对COVID-19整个病程与证候演变过程中的因时制宜以及辨证特色,从分子的视角阐释中医药不仅适用于疫病的预防,更有效于疫病的发生、发展以及微证转重过程,为中医药防治新型冠状病毒肺炎主要作用机制与靶点的阐明提供科学依据。

Objective To analyze and compare the different mechanisms of the corona virus disease 2019(COVID-19)prescriptions representing the mechanism of action of traditional Chinese medicine,in order to explain the mechanism of pharmacological action of traditional Chinese medicine in the prevention and treatment of novel coronary pneumonia. Methods According to the prescription of traditional Chinese medicine in the clinical treatment period of the Pneumonitis Diagnosis and Treatment Scheme for Novel Coronavirus Infection(Trial Version 6) issued by the National Health and Health Commission,four principle of treatments are summarized based on the evolution of disease syndromes,and each treatment is selected. The high-frequency and treatment-representing Chinese medicine constitutes a prescription collection. According to the principle of treatment,the SymMap database is searched and collected for each Chinese medicine target for analysis and induction. The STRING and DAVID software are used to analyze the GO biological process and enrichment analysis of KEGG signal pathway for each treatment target. Results The four types of treatment mainly involve cancer,virus infection,and various cytokines and immune regulatory pathways. However,the different prescriptions of each treatments have different characteristics. The specific manifestations are that dispersing cold and overcoming dampness,dispersing lung and relieving exterior is mainly used to restore the body’s homeostasis,regulates immunity to prevent further evolution of syndromes;clearing heat and removing dampness,clearing lung and detoxification mainly affects antiviral pathways such as inhibiting virus replication in the body and enhancing immune function;clearing Qi and cooling Ying,clearing heat and toxic is more concentrated in inhibiting inflammation and cell differentiation,anti-apoptotic pathways;complexing pulse and inducing resuscitation,this treatment is more focused on enhancing the positive regulation of the body. Conclusion The four types of treatment of non-classical prescriptions have proved the protection mechanism of TCM on the entire course of COVID-19 and the evolution of syndromes from different perspectives. From a molecular perspective,it explains that TCM is not only suitable for the prevention of epidemics,but also it is effective in the occurrence and development of epidemic diseases and the process from mild to severe,and provides a scientific basis for the prevention and treatment of COVID-19 by Chinese medicine.