[关键词]
[摘要]
目的 深静脉血栓是新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)危重症患者病亡和预后不佳的重要原因,挖掘中医药防治血栓的组方用药规律,为中医药用于防治COVID-19危重症患者出现深静脉血栓提供参考。方法 以中国知网和万方数据库收录的相关文献为资料来源,使用Excel 2010、Clementine 12.0软件,对纳入标准的中药进行关联规则分析,运用网络药理学的方法对核心药物组合进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,研究其作用机制并借助分子对接加以验证。结果 从中国知网和万方数据库中筛选出抗血栓方剂356个,发现25味高频中药,进一步关联分析得到7个高频药物组合。其中,核心药物组合“红花-桃仁-赤芍-川芎”的有效化学成分23个,核心药物组合与血栓的交集靶点41个,PPI网络主要涉及IL-6、VEGFA、CASP3、ALB、EGFR、MAPK8等关键靶蛋白,GO功能富集分析,得到生物过程条目971个(P<0.05),KEGG富集得到105条通路(P<0.05),主要涉及卡波济氏肉瘤疱疹病毒感染、人巨细胞病毒感染、流体剪切力和动脉粥样硬化、乙型肝炎等通路;分子对接筛选得到与IL-6结合能力较好的活性成分是木犀草素、槲皮素、黄芩素。结论 核心药物组合中的关键活性成分可通过调控IL-6等关键靶点,借助卡波济氏肉瘤疱疹病毒感染、人巨细胞病毒感染、流体剪切力和动脉粥样硬化、乙型肝炎等通路发挥抗血栓作用,为新冠肺炎危重症患者出现深静脉血栓的预防和治疗提供参考。
[Key word]
[Abstract]
Objective Deep venous thrombosis is an important cause of death and poor prognosis in critically ill patients with COVID-19. This paper excavates the prescription rules of TCM in preventing and treating thrombosis, so as to provide reference for Chinese medicine in preventing and treating deep venous thrombosis in critically ill patients with COVID-19. Methods Based on the journal literature collected from CNKI and Wan-fang database, excel 2010 and Clementine 12.0 software were used to analyze the association rules of the included standard traditional Chinese medicine, and analyze the enrichment of GO and KEGG in the core drug groups with the method of network pharmacology. The mechanism of action was studied and verified by molecular docking. Results A total of 356 antithrombotic prescriptions were screened from CNKI and Wan-fang database, 25 high-frequency herbs were found, and seven high-frequency drug groups were obtained by further correlation analysis. Among them, there were 23 effective chemical components in the core drug group "Honghua (Carthami Flos)-Taoren (Persicae Semen)-Chishao (Paeoniae Radix Rubra)-Chuanxiong (Chuanxiong Rhizoma)", 41 intersection targets between core drug group and thrombus. PPI network mainly involved key target proteins such as IL6, VEGFA, CASP3, ALB, EGFR, MAPK8, etc. Go functional enrichment analysis revealed 971 biological process entries (P<0.05), and 105 pathways (P<0.05) were obtained from KEGG enrichment, which mainly involved Kaposi's sarcoma herpes virus infection, human cytomegalovirus infection, fluid shear force, atherosclerosis, hepatitis B and other pathways. The results showed that luteolin, quercetin and baicalein were the active components with better binding ability to IL-6. Conclusion The key active components in the core drug group can play an antithrombotic role by regulating key targets such as IL-6, and by means of the pathways of Kaposi's sarcoma herpesvirus infection, human cytomegalovirus infection, fluid shear force, atherosclerosis, hepatitis B, etc., with view to providing a reference for the prevention and treatment of deep vein thrombosis in critically ill patients with COVID-19.
[中图分类号]
R285
[基金项目]
国家重大新药创制项目(2017ZX09301071);国家国际合作基地项目(2016-65)