Study On The Pattern And Mechanism Of Chinese Medicine Medication For Renal Anemia In Patients With ND-CKD Stage 3-5

Objective:The purpose of this study is to collect prescription information in the literature related to Chinese medicine for the treatment of renal anemia in non-dialysis CKD stage 3-5 patients in the past 20 years from three major databases,namely CNKI,VIP and Wanfang,in order to analyze the rules of medication and core drugs in the clinical management of renal anemia in Chinese medicine.And on this basis,use network pharmacology technology to explore the biological target and mechanism of action of the core drugs,to provide more ideas for the clinical treatment of renal anemia,and also to provide the theoretical basis for further experimental research in the later stage.Methods:1.The Chinese medicine prescriptions that met the inclusion criteria of this study were screened by collecting the relevant literature on the treatment of renal anemia in non-dialysis CKD stage 3-5 patients from the three major databases of CNKI,VIP and Wanfang over the past 20 years,and the drugs in the prescriptions were organized according to a uniform format and entered into Excel for analysis of frequency,drug use category and flavor and meridian tropism,next IBM SPSS Statistics 26.0,and IBM SPSS Modeler 18.0 softwares were used to analyze association rule analysis on drugs-drugs and system cluster.Finally,the analysis results were summarized and concluded.2.The core drugs were collected and screened by TCMSP database to find out the active ingredients,and the UniProt database was used to match the gene targets for the active components,and used the OMIM,Drugbank and GeneCards databases to screen out the disease target of renal anemia,and the intersection targets of drugs and disease was taken,used the STRING database to analyze the intersection targets to obtain protein interactions,and then the results were used to construct PPI network maps by Cytoscape 3.9.1.Finally,GO function and KEGG pathway enrichment analysis of the intersection targets were performed by Metascape database to explore the potential mechanism of core drugs in the treatment of renal anemia.Results:1.This study included 216 prescriptions,146 traditional Chinese medicines,and a total of 2374 times of use of traditional Chinese medicines.Traditional Chinese medicine with a usage frequency≥15 was defined as high-frequency traditional Chinese medicine,with a total of 35 drugs and a total usage frequency of 1904 times.In high-frequency traditional Chinese medicine,the frequency of use of Qi tonifying drugs was the highest;the medicinal properties of herbs were mostly warm and mild;the main flavor of medicinals was sweet;the high-frequency traditional Chinese medicine mainly focused on the kidney meridians,followed by the liver and spleen meridians.According to the analysis of association rules,the most commonly used drug pair was Astragalus-Angelica,and five new prescriptions were predicted through cluster analysis.Finally,based on multiple comprehensive analyses such as medication frequency,association rules,and clustering,the core drugs were determined as:Astragalus,Angelica,Poria cocos,Atracty lodes macrocephala,Rhubarb,Prepared rehmannia,Codonopsis pilosula,Ligusticum wallichii,Salvia miltiorrhiza,and Epimedium.2.Search the compound components of the core drugs in TCMSP yielded 178 active components,and after matching,248 drug related targets were obtained.The predicted drug target proteins were compared with 1186 target proteins associated with renal anemia,and 87 intersecting targets were obtained.The drug targets network was constructed and topological structure analysis was performed,after screening the results showed that the main active components of the drugs were quercetin,kaempferol,luteolin,tanshinone ⅡA,and so on.After screening,14 potential core targets of core drugs in the treatment of renal anemia were obtained,including AKT1,STAT3,TP53,HSP90A,STAT1,ESR1,HIF1A,MYC,EGFR,MAPK1,FOS,TNF,IL-10,and IL-6.GO functional enrichment analysis of intersection targets yielded 1784 results and KEGG enrichment analysis yielded 166 results.KEGG enrichment analysis showed that the important signal pathways related to the treatment of renal anemia by the core drugs included:cancer signal pathway,AGE-RAGE signal pathway in diabetes complications,HIF-1 signal pathway,PI3K-Akt signal pathway,TNF signal pathway,etc.Conclusion:1.The renal anemia is mostly caused by renal lesions involving other viscera,resulting in deficiency of qi,blood,yin and yang.After a long time,it is difficult to expel phlegm and toxin,obstructing the body,and affecting the production of qi and blood.Modern doctors often treat this disease with the main treatment methods of strengthening the spleen and kidney,supporting the righteousness and supplementing the deficiency,and flexibly add treatment methods such as removing blood stasis and discharging turbidity according to the different causes,pathogenesis,and pathological products,with both tonifying and purging application.2.According to the data association rules and cluster analysis,the core drugs concludes:Astragalus,Angelica,Pori a cocos,Atracty lodes macrocephala,Rhubarb,Prepared rehmannia,Codonopsis pilosula,Ligusticum wallichii,Salvia miltiorrhiza,and Epimedium.3.Research on network pharmacology has shown that drugs in the core drugs mainly contain active ingredients such as quercetin,kaempferol,luteolin,and tanshinone ⅡA,and these active ingredients mainly regulate the pathological progression of renal anemia through targets such as AKT1,STAT3,and TP53,and signal pathways such as AGE-RAGE,HIF-1,PI3K-Akt,and TNF interfere with the treatment of renal anemia,it reflects the mechanism characteristics of TCM with multi-component,multi-target and multi-pathway for the treatment of renal anemia.