丹参多酚酸B通过NLRP3/Caspase-1/GSDMD通路抑制OGD诱导海马神经元焦亡的分子机制研究

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[关键词]血管性痴呆;丹参多酚酸B;氧糖剥夺;细胞焦亡;NLRP3/Caspase-1/GSDMD信号通路；网络药理学[中图分类号]R285.5 [文献标志码]A [文章编号]doi：10.3969/j.issn.1674-070X.2025.04.008

[Abstract]Objective To explore thepotential molecular mechanisms of salvianolicacidB （Sal B）in treating vascular dementia（VD）throughnetworkpharmacologyandexperimentalverification.MethodsNetworkpharmacologywasusedto identifythepotentialargetsofalBinterventioninVD.Aprotein-proteininteraction（PP）networkwasonstructed，folloed by GO and KEGG pathwayenrichmentanalyses todetermine biologicallrelevant target pathways.Moleculardocking wasperfored toevaluate theinteractionbetweenSalBanditstargets.TheoptimalconcentrationofSalBwasdeterminedvia CCK-8assay thecellorphologywasobservedunderamicroscope，andthereleaserateoflactatedehydrogenase（LDH）inthecellsupeatant wasmeasuredusingamicroplatereader.The levelsof inflammatoryfactorsweremeasuredbyELISA，theproteinexpresionof NLRP3wasexaminedbyimmunofluorescence，andtheproteinexpresion levelsofNOD-likereceptorprotein3（NLRP3）， apoptosis-assiatedspck-likeproteinontainingaD（ASC）cysteinylaspartatespecifcproteinase1（Caspase-1），ndD werecheckedbyWesternblot.ResultsAtotalof37targetsforSalBinterventioninVDwereobtainedbybioinformatics analysis.CoretargetgenessuchasCaspase-1，NLRP3，andTNFR1werescreenedbynetwork pharmacologyandthepathways including theNOD-likereceptors（NLRs）signaling pathwaythatmayinvolvethesetargetgeneswereidentifiedthrough KEGG andGOanalyses.InvitroexperimentswereperformedusingtheclassicNLRP3/Caspase-1/GSDMDpyroptosispathway.The OGD-inducedpyroptosismodelofhippocampalneuronswasestablished，anditwasfoundthatSalBcouldsignificantly enhance the survival rate of HT22 cells after OGD （ P<0.05 ，P<0.01），alleviate cell damage，reduce LDH release （ P<0.05 or P<0.01 ） decrease the levels of IL- 1β and IL-18 in OGD-damaged HT22 cells （P<0.01），inhibit theactivation of NLRP3 inflammasome，and reduce the protein expression levels of NLRP3， GSDMD-N， cleaved Caspase-1，and ASC（ P <0.05，P

[Keywords]vascular dementia;salvianolicacid B; oxygen-glucose deprivation； pyroptosis;NLRP3/Caspase-1/GSDMD sig naling pathway; network pharmacology

血管性痴呆（vascular dementia，VD）是认知功能下降的常见原因，是第二大常见的痴呆类型，约占全球痴呆病例的 20%[2] ，世界卫生组织已将VD的防治列为21世纪重点科研项目之一[3-4]。（剩余14006字）