基于计算生物学的含何首乌中成药药物性肝损伤机制研究

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中图分类号：R285 文献标志码：A 文章编号：1002-4026（2025）04-0014-14

Abstract：Drug-inducedliver injury（DILI）is one of themost common adverse drug reactions.Therefore，using computational biologyandartificial inteligencemodeling toexplorethematerialbasisandmechanismsunderlyingadverse drugreactions fromtraditional Chinese medicine compoundsisof great significanceinenhancing thesafetyof clinical medication.Inthisstudy，weretrievedthechemicalcompostionandtargetinformationofCompoundPolygonummulifoum andRehmanna glutinosa Pils（CPRP），along withDILI-relatedtargets.ACPRP-DILIprotein-proteininteractionnetwork containing362nodesand1518interactions wasconstructedbasedonthis information.Geneontologyanalysis indicated that in terms of molecular function CPRP-DILIprimarily involves reactionstochemical substances，chemical stimuli，andorganic compounds.Cellular componentsare primarily localized to the extracelularregion，plasma membrane，and cellsurface.The biological processes of CPRP-DILIinvolve thebinding of enzymes，proteins，smallmolecules，and signaling receptors.Kyoto encyclopedia of genesandgenomes signaling pathway analysis revealed the involvement of the Pl3K-Akt and MAPK signalingpathways.The keymiRNAs inthe miRNAregulatory network include hsa-mir-34a-5pand has-mir-155-5p.The HubGenes of the two core subnetworks include AKT1，CTNNB1，MAPK3， HIF1A，JUN，TP53，and STAT3.The Clinical drugs associated withDILl includeantitumordrugs，nonsteroidalanti-nflammatorydrugs（NSAIDs），andimmunosuppressants. Fourteen high-risk DILIcompounds were predicted tobe present in CPRP，including emodin，rhein，andgalicacid.The chemicalcomponents in CPRP mayafect certain biological pathways in susceptible populations，interfering with hepatic angiogenesisandautophagybalance，therebyimpeding liverrepair processesand exacerbatingliver injury.Thechemical compoundsmayalsoexhibitcross-hepatotoxicitywith pyrimidine-containingantitumordrugs，NSAIDs，and immunosuppressants，suggesting thatcautionis needed when co-administering CPRP with the aforementioned drugs in clinical settings.

KeyWords：drug-induced liverinjury；Polygonummultiflorum；CompoundPolygonummulifoumandRehmannia glutinosa Pills； computational biology； angiogenesis

药物性肝损伤（drug-induced liver injury，DILI）是指药物在使用过程中，因药物本身或其代谢物或由于特殊体质对药物的超敏感性或耐受性降低所导致的肝脏损伤，亦称药物性肝病[1]。（剩余17662字）