基于网络药理学探讨白芍总苷治疗类风湿关节炎肺间质纤维化的机制研究  

Study on the Mechanism of Total Glucosides of Paeony in the Treatment of Pulmonary Interstitial Fibrosis in Rheumatoid Arthritis Based on Network Pharmacology

作　　者：邢清桦 李松伟[1,2,3] 龚晓红 胡文盈 陆超群 XING Qinghua;LI Songwei;GONG Xiaohong;HU Wenying;LU Chaoqun(Henan University of Chinese Medicine,Zhengzhou 450046,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan Province Hospital of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学,郑州450046 [2]河南中医药大学第一附属医院,郑州450000 [3]河南省中医院,郑州450000

出　　处：《中国畜牧兽医》2024年第2期850-863,共14页China Animal Husbandry & Veterinary Medicine

基　　金：2022年度省级科技研发计划联合基金(优势学科培育类)项目(222301420089);2022年河南省科技攻关项目(222102310392)。

摘　　要：[目的]通过网络药理学结合动物试验探究白芍总苷(TGP)主要药物成分与类风湿关节炎(RA)肺间质纤维化之间的作用靶点,揭示白芍总苷治疗RA肺间质纤维化的分子机制。[方法]通过检索多个数据库,根据2个ADEM参数口服生物利用度(oral bioavailability, OB)>30%、类药性(drug likeness, DL)>0.18,筛选出白芍总苷中的主要活性成分及作用的基因靶点;检索DrugBank、GeneCards、OMIM、TTD、DisGenet等数据库筛选RA和肺间质纤维化的基因靶点,通过UniProt数据库进行靶点蛋白的基因名转换,收集白芍总苷治疗RA和肺间质纤维化的作用靶点。获取化合物和疾病靶点取交集,制作韦恩图;将靶点交集导入到STRING数据库绘制PPI网络图,利用DAVID数据库进行GO功能和KEGG信号通路富集分析,深入分析其治疗类风湿关节炎合并肺间质纤维化的机制。将Wistar大鼠分为空白组、模型组、白芍总苷组和托法替布组,通过测定肺脏指数反映肺脏组织的水肿炎症反应,HE染色观察各组肺组织和踝关节滑膜租住的炎症反应,Masson染色观察肺脏组织的胶原沉积状况。[结果]检索TCMSP数据库,筛选得到85种白芍总苷的药物成分,根据OB>30%、类药性>0.18,共筛选9种主要成分;从DrugBank、DisGenet、OMIM、TTD和GeneCards等数据库筛选RA疾病靶点1 625个,肺间质纤维化的疾病靶点1 930个。通过GO功能和KEGG信号通路富集分析共获得分子功能65条目,细胞组分37条目,生物过程350条目和141个富集通路。通过中药-靶点-通路网络图,将Degree排名前十的肿瘤坏死因子(TNF)、白细胞介素-6(IL6)、AKT丝氨酸/苏氨酸激酶1(AKT1)、血管内皮生长因子A(VEGFA)、基质金属蛋白酶9 (MMP9)、转录因子Jun(JUN)、过氧化物酶体增殖物激活受体γ(PPARG)、胱天蛋白酶3(CASP3)、前列腺素内过氧化物合酶2(PTGS2)、细胞间黏附分子-1(ICAM1)作为白芍总苷治疗RA肺间质纤维化的关键作用靶点。动物[Objective]The aim of this experiment was to explore the targets and mechanisms between the main drug components of total glucosides of paeony(TGP)and pulmonary interstitial fibrosis in rheumatoid arthritis(RA)through network pharmacology.[Method]By searching multiple databases,according to two ADEM parameters of oral bioavailability(OB)>30%and drug likeness(DL)>0.18,the main active ingredients and gene targets of total glucosides of paeony were screened out.The gene targets of RA and pulmonary interstitial fibrosis were screened by searching DrugBank,GeneCards,OMIM,TTD,DisGenet and other databases.The gene names of target proteins were converted by UniProt database,and the targets of total glucosides of paeony in the treatment of RA and pulmonary fibrosis were collected.The intersection of ingredients and disease targets were obtained,Venn diagram was made.The target intersection was imported into the STRING database to draw the PPI network diagram,and the intersection was copied and pasted into the DAVID database for GO function and KEGG signaling pathway analysis,and the mechanism of its treatment of RA with pulmonary interstitial fibrosis was analyzed in depth.Wistar rats were divided into blank group,model group,total glycosides of peony group,and tofacitinib group.The lung index was measured to reflect the edema and inflammatory response of lung tissue,HE staining was used to observe the inflammatory response of lung tissue and ankle joint synovium in each group,and Masson staining was used to observe the collagen deposition in lung tissue.[Result]A total of 85 components of total glucosides of paeony were screened by searching the TCMSP database.According to OB>30%and DL>0.18,9 main components were screened.A total of 1625 RA gene targets and 1930 pulmonary interstitial fibrosis gene targets were screened from DrugBank,DisGenet,OMIM,TTD and GeneCards databases.A total of 65 terms of molecular functions,37 terms of cell components,350 terms of biological processes and 141 enrichment pathways were obtained b

关 键 词：网络药理学 白芍总苷 类风湿关节炎 肺间质纤维化 作用机制 

分 类 号：S853.74[农业科学—临床兽医学]