Exploring The Mechanism Of Jianpi Yiqi Fa Preventing And Treating Peritoneal Fibrosis Based On Data Mining And Network Pharmacology

Objective: Based on data mining and network pharmacology,the author studied the mechanism of invigorating spleen and qi to prevent Peritoneal dialysis-associated Peritoneal fibrosis(PF),and verified it by cell experiments.Methods: Through data mining "Chinese Medical Code" on the treatment of Qi deficiency syndrome related prescription information,analyze the law of invigorating spleen and qi.Based on Q-marker theory and relevant literature on blood components,the main effective components of Jianpi Yiqi Recipe were retrieved and their potential targets were predicted.The relevant targets of PF and qi deficiency syndrome were retrieved through GeneCards,DisGeNET and OMIM databases.veny diagram was used to screen out potential targets of Jianpi Yiqi Recipe related to Qi deficiency syndrome and PF,and to construct a Venn diagram of "target of effective components of compound--target of Qi deficiency syndrome--target of disease".The selected targets were uploaded to the STRING database,the TSV file was downloaded and imported into Cytoscape3.7.1 to make the PPI protein interaction network diagram for core target analysis.In the Metascape database,we can find the desired intersection targets and then analyze them using the GO and KEGG methods.Download the result files obtained from the analysis,and use them to draw the GO analysis diagram and KEGG signal pathway analysis diagram expressing the analysis results,and determine the key effective components according to the corresponding number of targets of Jianpi Yiqi Recipe and the relevant literature evidence of its anti-fibrosis.By conducting cell experiments on TGF-β1 induced peritoneal interstitial cell transdifferentiation,and observing the effects of Jianpi Yiqi Recipe on Cx43,Akt/mTOR pathway and Human peritoneal mesothelial cells(HPMCs)damage marker molecules.To clarify the effect and possible mechanism of Jianpi Yiqi Recipe regulating Cx43 to improve HPMCs injury,and to provide new ideas and methods for TCM prevention and treatment of PD-related PF.Results: 1.A total of 691 TCM prescriptions were selected for treating Qi deficiency syndrome.Among them,the main drugs used for qi deficiency disease were tonifying spleen and tonifying spleen,regulating qi and improving water and dampness.The top 10 Chinese herbs used frequently were glycyrrhiza licorice,atractyloides,ginseng,angelica sinensis,poria cocos,Tangerine peel,astragalus membranaceus,Bupleurum,xylosa and cohosh.Cluster analysis showed that the five core drug combinations with the effect of invigorating spleen and qi could be respectively ginseng,glycyrrhiza,atractyloides,tangerine peel,angelica and Astragalus.Paeony--Licorice--Angelica--Atractyloides--Poria cocos--Astragalus;Angelica sinensis--Poria cocos--Fructus aurantii--Pinellia pinellia--Tangerine peel;Poria cocos--Yam--alisma alisma--Atractylodes albatractylodes--Licorice--ginseng;Dried ginger-Aconite seed-cooked Rehmannia-licorice-Poria-Dendrobium,based on Sijunzi Decoction,revealed the drug law of invigorating spleen and invigorating qi.2.A total of 38 active ingredients of Jianpi Yiqi Recipe were screened by network pharmacology,corresponding to 648 drug targets;There were 612 targets related to PF and 2728 targets related to temper deficiency.There are96 common targets between active components and disease.Key targets such as ALB,VEGFA,TNF,IL6,AKT1 and IL1 B were determined by Cytoscape analysis.The core active components of drugs may be luteolin,quercetin,astragaloside IV,puerarin and glycyrtinic acid,etc.The GO analysis of Jianpi Yiqi Recipe in the treatment of PF with Qi deficiency syndrome showed that the top 3 biological processes were positive regulation of cell migration,lipopolysaccharide response and hormone response.The top 3 molecular functions were protein kinase activity,serine type peptidase activity and heme binding.Some of the top 3 concentrations were secretory granulosa,membrane raft and receptor complex.The concentration of KEGG signaling pathway indicated that the treatment of PF by Jianpi Yiqi recipe might be related to PI3K-Akt signaling pathway.PPI analysis of 96 targets and PI3K/Akt pathway indicated that Cx43 was closely related to the related targets of Jianpi Yiqi prescription in the treatment of PF with qi deficiency syndrome,and may play an important role in the process.3.The results of cell experiments showed that Jianpi Yiqi Recipe might interfere with the EMT process of peritoneal mesenchymal cells mediated by PI3K/Akt/mTOR signaling pathway by regulating Cx43 expression,so as to protect peritoneal mesenchymal cells and interfere with EMT process.Conclusion: Spleen and Qi strengthening is based on Sijunzi Decoction,while Jianpi Yiqi Recipe is a multi-component-multi-target-multi-pathway mechanism to prevent PF by interfering with Qi deficiency syndrome,and its key components may be luteolin,quercetin,astragaloside IV,puerarin,glycyrrhetinic acid,etc.The core targets of intervention may include ALB,IL6,TNF,VEGFA,AKT1 and IL1 B.Cx43 and PI3K/Akt signaling pathways are closely related to the intervention of Jianpi Yiqi Recipe in the treatment of PF with Qi deficiency syndrome.Jianpi Yiqi Recipe may interfere with the EMT process of peritoneal mesenchymal cells mediated by Akt/mTOR signaling pathway by regulating Cx43 expression,so as to play a role in protecting peritoneal mesenchymal cells and interfering with EMT process.