大麻二酚经PERK-eIF2α-ATF4-CHOP通路减轻多重脑震荡大鼠的神经元內质网应激和凋亡

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Abstract：ObjectiveToexploretheefectsofcannabidiolonendoplasmicreticulumstressandneuronalapoptosisinratswith multiple concussons （MCC）. Methods SD rats were randomized into sham group，MCC group， 1% tween20 （TW） treatment group，and low-dose （10mg/kg） andhigh-dose （40mg/kg ）cannabidiol treatment groups.Inallbut the sham group，MCC modelswereestablished usingametal pendulum percusiondevice，after which theratsreceiveddaily intraperitoneal injectionsoftfks.essfF，-d 3inthebraintisueof theratsweredetectedwithqRT-PCR，Westernblotingandimmunofluorescencestaining.Thecore targetsofcannabidiolintreatmentof traumaticbraininjury（TBl）wereidentifiedbynetworkpharmacologyanalysis，and moleculardocking wascarriedouttosimulatetheinteractionofcannabidiol withthefactorsrelated toendoplasmicreticulum stressandapoptosis.ResultsComparedwiththesham-operatedrats，theratmodelsofMCCshowedsignificantlyincreased mRNA expressonsofERK，eF2αandCHOPandproteinexpressionsofERK，e2a，A4，HOPB3，p-Adp caspase-3inthecerebalcortex.CBDtreatment，especiallyattheghdoseobviouslyicreasedtheexpresionof p-Atand loweredtheexpressonlevelsoftheotherfactorstestedintheratmodels.Network pharmacologyanalysisindicated interactionsoftecoretargetsofCDwiththctorselatedtoedoplasmiceiculumstressandTndmolecuardocing study showed ahigh binding energy ofCBD with multiple factors pertaining toendoplasmic reticulum stressand apoptosis. ConclusionMCCinduceendoplasmic reticulum stressandapoptosis inratbraintisues，forwhich CBD，especiallyatahigh dose，provides neuroprotective effects by inhibiting endoplasmic reticulum stressand cell apoptosis.

vords：multiplecerebralconcussions;cannabidiol;endoplasmicreticulumstres;neuronalapoptosis;PERK signalingpa

脑震荡（CC）是在外力作用下引起神经组织结构和功能紊乱的轻型创伤性脑损伤（mTBI），主要发生在竞技类体育项目和意外事故中，可导致严重的神经损伤，产生认知障碍和抑郁、焦虑等精神疾病，给患者及家庭带来严重困扰2。（剩余14964字）