金丝桃苷对氧糖剥夺再灌注致皮层神经元损伤保护作用及其机制-protective effect of hyperoside on cerebral cortex neurons damage caused by oxygen-glucose deprivation and reperfusion and its mechanism.docxVIP
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金丝桃苷对氧糖剥夺再灌注致皮层神经元损伤保护作用及其机制-protective effect of hyperoside on cerebral cortex neurons damage caused by oxygen-glucose deprivation and reperfusion and its mechanism
PartIIProtectivemechanismsofhyperosideoxygen-glucosedeprivation-reperfusion-inducedcorticalneuroninjuryBackgroud:Nitricoxide(NO)isanimportantmessengermoleculeinvolvedinmanyphysiologicalandpathologicalprocesses.PreviousstudieshaveshownthatNOconcentrationsinthebrainareincreasedandtheexcessiveproductionofNOcontributestocellsdeath.WehaveknownthatNOmediatesthedownstreamsignaltransductionofvariousneurotoxinsleadingneuronalinjuries.TheinhibitionofNOgenerationcanreducetheinfarctsizeofthebraincausedbymiddlecerebralarteryocclusion(MCAO)inrats,andNOscavengerssignificantlyreducecelldeath.PreviousstudiesshowthathyperosidehasinhibitoryeffectonNOproduction.WeaskwhetherNOisinvolvedintheneuroprotectiveeffectsofhyperoside.Methods:Intracellularcalciumconcentration([Ca2+]i)wasmonitoredusingthefluorescentCa2+indicatorFura-2/AMbycalciumimagingtechnique.TheexpressionsofNO-relatedsignalingpathwayproteinsandapoptosis-relatedproteinsweremeasuredbywesternblotting.CytoimmunityfluorescencewereemployedtoevaluateactivationofNF-κB.Results:TheelevationofNMDA-induced[Ca2+]iwasalsoattenuatedbyhyperoside.PhosphorylationofCaMKIIwasinhibitedbyhyperoside.Meanwhile,hyperosidelessenediNOSexpressioninducedbyOGD-R,whichmaybemediatedbyinhibitionofNF-κBactivation.ERK,CREB,JNKandBcl-2family-relatedapoptoticsignalingpathwaywasinvolvedintheneuroprotectionaffordedbyhyperoside.Conclusion:OurstudyindicatedthathyperosideprotectedagainstOGD-Rinjurythroughattenuationofintracellularcalciumoverload,downregulationofp-CaMKIIexpressionandinhibitionofNF-κBactivation,downregulationp-JNKandpro-apoptoticproteinBaxexpression,upregulationp-ERK,p-CREBandanti-apoptoticproteinBcl-2expression.AllofthesepathwaysarerelatedtoNO,indicatingthattheregulationofNOsignalingpathwayplaysimportantrolesintheneuroprotectiveeffectsofhyperoside.Keyword:Hyperosode;Corticalneuron;Oxygen-glucosedeprivation-reperfusion;Nitricoxide缩略词表(abbreviation)ACSFartificialcerebrospinalfluid人工脑脊液[Ca2+]iintracellularfreecalciumconcentration胞内游离钙离子浓度Ca2+/CaMcalcium/c
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