皮肤性病诊疗学杂志2024，Vol.31Issue(5)：303-312,10.DOI:10.3969/j.issn.1674-8468.2024.05.003
益气活血复方治疗硬皮病肺部炎症与纤维化的作用机制:基于生物信息学与网络药理学方法
The mechanisms by which Yiqi Huoxue compound treats pulmonary inflammation and fibrosis in scleroderma:Based on bioinformatics and network pharmacology
摘要
Abstract
Objective To identify the effective components and key molecules of Yiqi Huoxu compound(YQHX)in the treatment of pulmonary inflammation and fibrosis in scleroderma,provi-ding basis for the development of drug targets for scleroderma.Methods A mouse model of pul-monary fibrosis was established by a single tracheal perfusion of bleomycin.Twenty-four mice were randomly divided into four groups,i.e.intragastric PBS,bleomycin alone,intragastric Yiqi Huoxue compound,and control.HE staining and Masson staining were used to verify the thera-peutic effect of Yiqi Huoxue compound on lung inflammation and fibrosis.The active components and target genes of anti-fiber salvia miltiorrhiza were obtained from TCMSP database.PPI net-work,GO/KEGG enrichment analysis,molecular docking and other bioinformatics analyses were integrated to identify the main active ingredients and key targets of salvia miltiorrhiza in the treat-ment of scleroderma,and to analyze the relevant signaling pathways.The expression levels of CD3 antibody,p-PI3K antibody and p-AKT antibody were analyzed by immunohistochemistry to verify the effects of Yiqi Huoxu compound on inflammation and key pathways.Results The results of HE staining and Masson staining showed that the severity of fibrosis and inflammatory infiltration were decreased,suggesting that Yiqi Huoxue compound could significantly improve the pulmonary fibrosis,inflammation and tissue damages.The key component of salvia miltiorrhiza was mainly luteolin.PPI network analysis showed that AKT1,EGFR,ESR1,TNF and IL6 were the core tar-gets of salvia miltiorrhiza in the treatment of scleroderma.KEGG enrichment analysis showed that the genes were mainly enriched in the PI3K-AKT pathway.Molecular docking analysis showed the potential binding sites between luteolin and four key targets.The immunohistochemical results showed that YQHX significantly decreased bleomycin-induced CD3+T cell infiltration,p-PI3K and p-AKT levels in mouse lung tissue.Conclusions YQHX has significant therapeutic effects on lung inflammation and fibrosis.Luteolin may be a key effective molecule in YQHX,and treat scleroderma lung inflammation and fibrosis by targeting the PI3K-AKT pathway.关键词
系统性硬化症/益气活血复方/丹参/肺纤维化/肺部炎症Key words
systemic sclerosis/Yiqi Huoxue Compound Formula/Danshen/pulmonary fibrosis/lung inflammation引用本文复制引用
胡梦华,孔祥贞,谭乔瑞,濮伟霖,杜敏,屠文震,孙大燕,杨婧漪,顾逸飞,王久存..益气活血复方治疗硬皮病肺部炎症与纤维化的作用机制:基于生物信息学与网络药理学方法[J].皮肤性病诊疗学杂志,2024,31(5):303-312,10.基金项目
中国医学科学院院外创新单元项目(2019-I2M-5-066) （2019-I2M-5-066）
