基于网络药理学探讨健脾疏肝方治疗非酒精性脂肪性肝病作用机制OA

Objective To explore the mechanism of Jianpi Shugan Prescription in the treatment of non-alcoholic fatty liver disease(NAFLD)based on network pharmacology,molecular docking technology and experimental verification.Methods The chemical components and corresponding targets of Jianpi Shugan Prescription were retrieved through the TCMSP database;Disease targets of NAFLD were retrieved from GeneCards,OMIM and DisGeNET databases.The intersection target of disease and drug was uploaded to the STRING 12.0 platform to obtain protein interaction information,and analyzed by Cytoscape 3.7.1 software to extract the core targets.The GO and KEGG pathway enrichment of intersection targets were analyzed using Metascape database.AutoDock Tools 1.5.6 software was used for molecular docking.NAFLD model was established.The rats were randomly divided into control group,model group,simvastatin group and Jianpi Shugan Prescription high-and low-dosage groups,and were given corresponding drugs by gavage for 6 weeks.The levels of serum lipid-related indexes(TC,TG,LDL-C,HDL-C)and liver function-related indexes(ALT,AST)were determined.Western blot was used to detect the protein expressions of the main pathway.Results Network pharmacology method screened out 145 targets of Jianpi Shugan Prescription in the treatment of NAFLD,and AKT1,TNF,IL6,IL1B,TP53,PPARG,HIF1A,MMP9,VEGFA and others were the core targets.KEGG pathway enrichment analysis showed that Jianpi Shugan Prescription played a therapeutic role mainly through PI3K-Akt signaling pathway and HIF-1 signaling pathway.The results of animal experiments showed that compared with the model group,the contents of serum TC,TG,LDL-C,ALT and AST in the Jianpi Shugan Prescription high-dosage group and simvastatin group significantly decreased(P<0.01),while the content of HDL-C increased(P<0.05,P<0.01).The protein expressions of p-AKT/AKT,PI3K,mTOR,HIF-1α and VEGFA in liver tissue of rats in Jianpi Shugan Prescription high-and low-dosage groups,and simvastatin group significantly decreased(P<0.01),and the protein expressions of p-AKT/AKT,HIF-1α and VEGFA in Jianpi Shugan Prescription high-dosage group were better than those in simvastatin group(P<0.01).Conclusion Jianpi Shugan Prescription has the characteristics of multi-component,multi-target and multi-pathway in the treatment of NAFLD.Its mechanism may be related to inhibiting the expressions of PI3K/AKT/HIF-1α signaling pathway related proteins and reducing liver lipid accumulation,thus playing a role in the treatment of NAFLD.