Exploration On The Mechanism Of Jiawei Sanbi Decoction In Alleviating Intervertebral Disc Degeneration Based On Network Pharmacology Combined With Data Mining

Objective:To explore the targets of Intervertebral Disc Degeneration(IDD)using gene chip-based data mining,and investigate the mechanism of Jiawei Sanbi Decoction in alleviating IDD using network pharmacology based on the clinical experience of adviser in the treatment of IDD-related diseases.Methods:IDD-related original data set was selected from the GEO database.Normalization was processed by the RMA method using R,missing values were processed by the KNN method,batch effect was removed using the Combat function,and differentially expressed genes were analyzed and calculated using limma package,to screen the highly differentially expressed genes meeting "FDR<0.005,|log2FC|>2"as direct targets.In addition,the effective components and direct targets of Jiawei Sanbi Decoction were screened using online databases including TCMSP,Pubchem and Uniprot.PPINs was constructed using Bisogenet to predict indirect targets.The intersection of the PPIN targets of Jiawei Sanbi Decoction and IDD was combined,and the key targets were mined according to 6 network topology parameters including DC,BC,CC,EC,LAC and NC.The key targets were subjected to GO and KEGG pathway enrichment by R,and the "target-pathway”network was constructed to screen the core effective targets of Jiawei Sanbi Decoction in alleviating IDD.Results:In this study,a total of 252 highly differentially expressed genes in IDD were mined based on GSE23130、GSE27494、GSE41883 and GSE15227 in the GEO database,including 222 up-regulated genes and 30 down-regulated genes.A total of 6,006 IDD-related targets were obtained(including 252 direct targets and 5,754 indirect targets).A total of 256 effective components and 7,021 targets of Jiawei Sanbi Decoction were obtained(including 284 direct targets and 6,812 indirect targets).A total of 296 key targets for Jiawei Sanbi Decoction alleviating IDD and their interaction networks were extracted after combining the PPINs of Jiawei Sanbi Decoction and IDD.Through the following GO and KEGG biological analysis,it was found that Jiawei Sanbi Decoction could alleviate IDD by regulating 7 core targets including TP53,AKT1,IKBKG,MAPK1,EGFR,NTRK1 and RELA to interfere with NF-κB,MAPK,PI3K-AKT and p53 pathways.Conclusion:The results of this study verify the overall regulatory characteristics of Jiawei Sanbi Decoction,including multi-component,multi-target and multi-pathway.It may alleviate the procession of IDD by resisting senescence,apoptosis and inflammation,regulating cell secretion,promoting ECM synthesis and regulating autophagy of the intervertebral disc tissue.This study provides a theoretical basis for later experimental research.