大鼠脑缺血预处理的神经保护作用与调节核因子-κB、Hes1及Bcl-2表达的研究

大鼠脑缺血预处理的神经保护作用与调节核因子-κB、Hes1及Bcl-2表达的研究大鼠脑缺血预处理的神经保护作用与调节核因子-κB、Hes1及Bcl-2表达的研究

摘要：缺血性脑卒中是一种突发性脑功能障碍的疾病，目前尚无有效的治疗方法。因此，寻找新的治疗方法具有重要意义。本研究旨在探讨大鼠脑缺血预处理对神经保护作用及其对调节核因子-κB、Hes1及Bcl-2表达的影响。采用大鼠脑缺血模型，采用免疫组化、Westernblotting等方法进行实验观察。实验结果表明，大鼠脑缺血预处理后，缺血-再灌注对脑损伤的影响减轻，神经损伤减轻，细胞凋亡减少，细胞存活率提高。同时，核因子-κB、Hes1及Bcl-2的表达水平均发生改变，预处理组示，核因子-κB、Hes1的表达均下调，Bcl-2的表达上调。因此，大鼠脑缺血预处理对神经保护有一定作用，其调节核因子-κB、Hes1及Bcl-2表达可能是其中一种机制。

关键词：脑缺血；神经保护；核因子-κB；Hes1；Bcl-Introduction:

Ischemicstrokeisasuddenonsetofbraindysfunctionandcurrently,thereisnoeffectivetreatmentavailable.Therefore,findinganewtreatmentmethodisofgreatsignificance.Thisstudyaimstoexploretheneuroprotectiveeffectoftheratbrainischemicpretreatmentanditseffectontheregulationofnuclearfactor-κB,Hes1,andBcl-2expression.

Methods:

Theratbrainischemiamodelwasused,andexperimentalobservationswereconductedusingimmunohistochemistry,Westernblotting,andothermethods.

Results:

Afterratbrainischemiapretreatment,theeffectofischemia-reperfusiononbraindamagewasreduced,thedegreeofneuralinjurywasreduced,apoptosiswasreduced,andcellsurvivalratewasincreased.Meanwhile,theexpressionlevelsofnuclearfactor-κB,Hes1,andBcl-2havebeenchanged.Inthepretreatmentgroup,theexpressionlevelsofnuclearfactor-κBandHes1weredown-regulated,whileBcl-2expressionlevelwasup-regulated.

Conclusion:

Theratbrainischemiapretreatmenthasacertaineffectonneuroprotection,andtheregulationofnuclearfactor-κB,Hes1,andBcl-2expressionmaybeoneofthemechanismsAdditionally,thefindingsofourstudysuggestthatischemicpreconditioningmayhaveapotentialtherapeuticeffectinthetreatmentofcerebralischemia.Thedown-regulationofnuclearfactor-κBandHes1expressionlevels,aswellastheup-regulationofBcl-2,maycontributetotheneuroprotectiveeffectofischemicpreconditioning.

However,furtherresearchisneededtofullyunderstandtheunderlyingmechanismsofneuroprotectioninducedbyischemicpreconditioning.Additionally,theoptimalpreconditioningprotocol,includingthenumberofcycles,duration,andtimingofischemicepisodes,remainstobedetermined.

Nevertheless,ourstudyprovidesevidenceforthepotentialuseofischemicpreconditioningasaneuroprotectivestrategyinthetreatmentofcerebralischemia.Byunderstandingthemolecularmechanismsinvolvedinthisprocess,wecandevelopmoreeffectiveandtargetedtreatmentstoimproveclinicaloutcomesforpatientswithstrokeandotherischemicbraininjuriesInadditiontoischemicpreconditioning,otherstrategiesforneuroprotectioninthetreatmentofcerebralischemiahavealsobeenexplored.Oneapproachisneuroprotectionthroughtheuseofpharmacologicalagents.Numerousdrugshavebeenstudiedfortheirabilitytoprotectthebrainagainstischemicinjury,includingN-methyl-D-aspartate(NMDA)receptorantagonists,calciumchannelblockers,andantioxidants.However,despitepromisingpreclinicalresults,fewofthesedrugshavebeensuccessfullytranslatedintoclinicalpractice,likelyduetothelimitedefficacyandsafetyconcerns.

Anotherpotentialstrategyforneuroprotectionistheuseofstemcells.Stemcellshavetheabilitytodifferentiateintovariouscelltypesandpossessimmunomodulatoryproperties,makingthemapromisingtherapeuticoptionforischemicbraininjury.Preclinicalstudieshaveshownthatvarioustypesofstemcells,includingmesenchymalstemcellsandneuralstemcells,canimproveneurologicalfunctionandreduceinfarctsizeaftercerebralischemia.However,furtherstudiesareneededtodeterminetheoptimalcelltype,routeandtimingofadministration,andmechanismsofaction.

Inaddition,non-invasivebrainstimulationtechniques,suchastranscranialmagneticstimulationandtranscranialdirectcurrentstimulation,havealsobeeninvestigatedaspotentialneuroprotectivestrategies.Thesetechniqueshavebeenshowntomodulatecorticalexcitabilityandenhanceneuralplasticity,andmayhavetherapeuticbenefitsinthetreatmentofstrokeandotherformsofbraininjury.However,furtherstudiesareneededtodeterminetheoptimalstimulationparametersandmechanismsofaction.

Inconclusion,ischemicstrokeisadevastatingneurologicalconditionwithlimitedtreatmentoptions.Whilecurrenttherapiesfocusedonrestoringbloodflowhaveshownsomebenefit,neuroprotectionstrategiesaimedatpreservingbraintissueareneededtoimproveoutcomes.Ischemicpreconditioning,pharmacologicalagents,stemcells,andnon-invasivebrainstimulationtechniquesareallpromisingapproachesthatwarrantfurtherinvestigation.DevelopingeffectiveandtargetedneuroprotectivetherapieswillbecriticaltoimprovingoutcomesforpatientswithcerebralischemiaEffectiveandtargetedneuroprotectivetherapiesarecriticaltoimprovingoutcomesforpatientswithcerebralischemia.Currenttherapiesfocusedonrestoringbloodflowha