丹參多酚酸B通過NLRP3/Caspase-1/GSDMD通路抑制OGD誘導(dǎo)海馬神經(jīng)元焦亡的分子機(jī)制研究

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[關(guān)鍵詞]血管性癡呆;丹參多酚酸B;氧糖剝奪;細(xì)胞焦亡;NLRP3/Caspase-1/GSDMD信號(hào)通路；網(wǎng)絡(luò)藥理學(xué)[中圖分類號(hào)]R285.5 [文獻(xiàn)標(biāo)志碼]A [文章編號(hào)]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

血管性癡呆（vascular dementia，VD）是認(rèn)知功能下降的常見原因，是第二大常見的癡呆類型，約占全球癡呆病例的 20%[2] ，世界衛(wèi)生組織已將VD的防治列為21世紀(jì)重點(diǎn)科研項(xiàng)目之一[3-4]。（剩余14006字）