党参-茯苓配伍调控ERα/PI3K/Akt信号通路改善单侧颈总动脉 永久结扎痴呆大鼠的认知障碍

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Abstract： Objective To investigate the mechanism of Radix codonopsis combined with Poria （CRP）for improving cognitive impairmentinduced bypermanentunilateralcommoncarotidarteryligation （UCCA）inrats.Methods UPLC-Q-TOF-MS/MS andnetworkpharmacologyanalysis wereused toanalyzethecomponents ofCRPinthebloodandbrainofrats medicated withCRP.RatmodelsofUCCAweretreatedwithCRPgavagefor1month，andMorriswatermaze，HEstainingandNeuN stainingeresdtossssaeticacy.aboloicslysisostostrydte blotingwereemployedtoexploreandvalidatethetherapeuticmechanismofCRP.ResultsAtotalof125chemicalconstituents wereidentifiedinthebraintissue（89Radixcodonopsiscomponentsand36Poriacomponents）and126inbloodsamples（85 Radix codonopsis components and 41Poria components）of medicated rats.Network pharmacologyanalysis revealed that the therapeuticmechanismofCRPondementiainvolvedprimarilythePI3K/Aktsignalingpathwayregulatedbythebraintargeting constituentsofCRP.InUCCArats，CRPtreatmentsignificantlyimproved their performance inMorris watermaze test，allevitedneuronal damageintheippocampusandcortexandincreasedexpresion levelof NeuN.Metabolomics analysis revealed significant enrichment of the estrogen and GABAergic synapse signaling pathways in CRP-treated rats. CRP

obviouslyreducedthebrain levelsofglutamateand GABA/glutamatein UCCA rats，anddownregulated the proteinsexpressionsofERα，p-PI3K/PI3Kand p-Akt/Akt. Conclusion CRP improves learning and memory impairmentin UCCAratspossiblybymodulatingthe ERα/PI3K/Akt signalingpathwayin thebrain. Keywords：compatibilityofRadixcodonopsisandPoria; dementia; permanent unilateral common carotid artery ligation; GABA; ERα/PI3K/Akt signaling pathway

随着经济的持续增长与社会人口结构的显著变迁，老年相关疾病问题日益受到关注。（剩余14631字）