莱菔硫烷通过抑制Aβ42寡聚体激活的U87细胞中MAPK/NF-κκκ 信号通路降低反应性星形胶质细胞介导的SH-SY5Y凋亡
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Abstract：ObjectiveToexploretheeffectsofsulforaphane（SFN）onAβ42-activatedU87astrocyte-mediatedapoptosisof SHSY5Yneuronsinvitro.MethodsU87cellstreatedwithdifferentconcentrationsofAβ42，SFNorbothwereexaminedfor changes incell activity， IL-6and TNF- α mRNA expression，release of IL-6and NF- α proteins， and expressions of p-p38， p-p65 andGFAPusingCCK-8assay，RT-qPCR，ELISAandWesternbloting.SH-SY5Yneuons wereco-culturedwithU87strocytes treated with Aβ42 alone or in combination with SFN or SB203580 for 24h， and the changes in Bax protein expression levels and viabilityofS-Ycellwereexamined.eeectsofAβ42SFN，ndteirombationwerealsoseredinstrotes isolated frommouse bain tisues，andthe indirect effectsof astrocyte treatmenttonviabilityof theco-cultured prmary neuronswereassessed.ResultsTheviabilityofU87astrocytesincreased significantly folowing treatmentwith 1.25μmol/L Aβ 42but decreased after Aβ42 treatment above 5μmol/L .SFN treatments for 24h below 5μmol/L did not significantly affect U87 cellviability.Aβ42treatmentsignicantlyieasedprteinexpressionsof-p38，p-p65andGFAPRNAexpressionvelsof IL-6and TNF- α， and IL-6 and TNF- α levels in culture supernatant of U87 cells. SH-SY5Y cells co-cultured with Aβ42-treated U87cellshowedsignificantlyincreasedproteinexpresionsofBaxandexhbitedloweredviabilityfollowingcoulurewith 5μmol/L Aβ42-treated U87 cells. The isolated mouse astrocytes showed lowered viability following Aβ42 treatment above 10μmol/L， butSFN treatment below 5μmol/L for24 did not obviously affect the cell viability.The primary neurons cocultured with Aβ42-treated mouse astrocytesshowedsignificantlylower cellviability thanthoseco-cultured with the astrocytes treated with Aβ+SFN or Aβ+SB203580 ！Conclusion SFN attenuates astrocyte-mediated neuron apoptosis by inhibiting the MAPK/NF-kB signaling pathway in Aβ42 oligomer-activated astrocytes
Keywords： sulforaphane;Alzheimer's disease; astrocyte; β -amyloid; MAPK; nuclear factor-kB; neuroinflammation; apoptosis
随着人口结构转变和社会经济变革，阿尔茨海默病（AD）及相关认知障碍的负担急剧增加，对公共卫生和经济产生了重大影响。（剩余17429字）