简介：MitochondrialK+-ATP(mito-KATP)channelsplayanimportantroleincellularfunctionandsurvivalfollowingischemicstress.Thepresentresultsrevealedthatinterventionwithdiazoxide,amito-KATPchannelopener,ledtoanincreaseinBcl-2expressioninthecerebralcortexofratssubjectedtocerebralischemiareperfusioninjury.Inaddition,theinterventionalsoledtoclearimprovementsinneuronalmitochondrialmorphologyandconsciousnesspost-injury.Glibenclamide,amito-KATPchannelblocker,exhibitedtheconverseeffects.Bothdiazoxideandglibenclamideexerteddose-dependenteffects(inparticular,at18mg/kgdiazoxideand25mg/kgglibenclamide).Thesefindingssuggestthatdiazoxideexertsaneuroprotectiveeffectoncerebralischemiareperfusioninjurybyopeningmito-KATPchannelsandupregulatingBcl-2expression.

简介：BACKGROUND:Previousstudieshaveshownthatthemitochondrialstructureandfunctionaredamagedinanimalmodelsofepilepsy.Inaddition,theBcl-2proteiniscapableofregulatingmitochondrialstability.OBJECTIVE:ToobserveandvalidatechangesinmitochondrialstructureandBcl-2expression,andtoanalyzethesecharacteristicsinthehippocampalCA3regionofratmodelsofepilepsy.DESIGN,TIMEANDSETTING:Thisrandomized,controlled,animalexperimentwasperformedattheLaboratoryofElectronMicroscopyandDepartmentofHistologyandEmbryology,LuzhouMedicalCollegebetween2007and2008.MATERIALS:CoriamyrtinwasprovidedbythePharmacyFactoryofWestChinaUniversityofMedicalSciences.TheprimaryandsecondaryantibodieswereprovidedbyZhongshanGoldenbridgeBiotechnology,Beijing.METHODS:Atotalof44adult,male,SpragueDawleyratswererandomlydividedintocontrol(n=11)andepilepsy(n=33)groups.Ratsintheepilepsygroupwereinducedbycoriamyrtin(50μg/kg),whichwasinjectedintothelateralventricles.Theratswerethenobservedat3,6,and24hoursafterepilepsyinduction,with11ratsateachtimepoint.Epilepsywasnotinducedinratsfromthecontrolgroup.MAINOUTCOMEMEASURES:PathologicalchangesinthehippocampalCA3regionwereobservedbylightmicroscopy;Bcl-2expressionwasanalyzedbyimmunohistochemistry;andmitochondrialchangesinthehippocampuswereobservedundertransmissionelectronmicroscopy.RESULTS:(1)ThecontrolgroupdisplayedverylittleBcl-2proteinexpressioninthehippocampalCA3region.However,after3hoursofepilepsy,expressionwasvisible.By6hours,expressionpeakedandthensubsequentlydecreasedafter24hours,butremainedhigherthanthecontrolgroup(P<0.05).(2)Mitochondriaweredamagedtovaryingdegreesintheepilepsygroups.Forexample,mitochondriaedema,cristaespaceincrease,anddisappearanceofmitochondriawereapparent.Moreover,mitochondrialdamageoccurredpriortopathologicalchangesintheneuronsandnucleolus.CONCLUSION:

简介：Inthisstudy,wesoughttoelucidatetheeffectsofmelatoninonlearningandmemoryaswellasapoptosisandexpressionoftheBaxorBcl-2proteinsinthesubgranularzoneofthedentategyrusinpinealectomizedrats.UsingtheMorriswatermazeandtheolfactorymemorytests,wefoundthattheaverageescapelatencyinpinealectomizedratswasclearlyincreasedcomparedwithsham-operatedrats.Moreover,theaverageescapelatencyinthemelatonin-treatedandpinealectomizedratswaslongerthanthatinthesham-operatedratsandshorterthanthatinthepinealectomizedanduntreatedrats.Immunohistochemistryandterminal-deoxynucleoitidyltransferasemediatednickendlabeling(TUNEL)showedthattherewerefewerBaximmunoreactivecellsandTUNEL-positive(apoptotic)cellsbutmoreBcl-2immunoreactivecellsinthemelatonin-treatedratscomparedwiththepinealectomizedrats.Thesham-operatedratsshowednumbersofthesecellssimilartothemelatonin-treatedrats.TheseexperimentalfindingsdemonstratethatmelatonintreatmentmayreduceabnormalapoptosisbypromotinggeneexpressionofBaxandsuppressinggeneexpressionofBcl-2inthesubgranularzoneofthedentategyrusinpinealectomizedrats.Theseeffectsappeartoresultintheinhibitionofcellularapoptosisandtheimprovementofspatiallearningandmemoryinpinealectomizedrats.

简介：目的探讨纳洛酮对脑缺血再灌注的神经保护机制.方法采用线栓法制造的大鼠局灶性脑缺血再灌注模型,通过免疫组化法检测脑缺血不同再灌注时间以及经纳洛酮(5mg/kg)预处理后bcl-2和c-fos蛋白的表达.结果脑缺血30min再灌注6h,bcl-2和c-fos蛋白表达显著增加;再灌注24h,bcl-2蛋白持续增高,而c-fos蛋白基本降至正常.表明纳洛酮可显著上调脑缺血后bcl-2蛋白的表达,抑制c-fos蛋白的表达.结论纳洛酮的神经保护机制可能与其上调bcl-2蛋白,抑制c-fos蛋白表达有关.

简介：目的探讨小鼠脑室管膜bcl-2和caspase-3在低氧预适应中的表达变化。方法将Blb／c近交系小鼠随机分为空白对照组（H0组）、低氧对照组（H1组）和低氧预适应组（H4组）。用免疫荧光和激光共聚焦显微镜等技术，测定bcl-2和caspase-3表达的荧光强度。结果H1和H4组的bcl-2表达均显著高于H0组，其中H4组又显著高于H1组。H1和H4组caspase-3的表达显著高于H0组，H4组显著低于H1组。结论低氧预适应过程中，小鼠脑室管膜区通过bcl-2的高表达和caspase-3的低表达，抵御室管膜细胞凋亡，参与脑保护机制。

简介：目的探讨氧增强放疗对胶质瘤凋亡相关基因Bcl-2、Bax影响的差异.方法建立大鼠胶质瘤动物模型,治疗组10只,高压氧处理后放疗;对照组10只,常规放疗.免疫组化检测凋亡相关基因Bcl-2、Bax的表达.结果治疗组Bcl-2表达明显低于对照组,组间差异有显著性（P＜0.05）;治疗组Bax的表达明显高于对照组,组间差异有显著性（P＜0.05）.结论氧增强放疗可以更有效地抑制Bcl-2、增加Bax的表达.

简介：目的探讨大鼠脑缺血再灌流后Bcl-2蛋白、Caspase-3mRNA的表达及炎性细胞漫润与神经细胞凋亡的关系.方法将54只Wistar大鼠随机分为二组:假手术组,缺血再灌流组.采用原位末端标记(TUNEL)、免疫组化和原位杂交技术分别观察脑缺血再灌流后不同时间点神经细胞凋亡及损伤的变化与Bcl-2、Caspase-3mRNA表达.结果Bcl-2表达于缺血再灌流12～24h达高峰,再灌流2～4d呈下降趋势,至16d略高于假手术组;Caspase-3mRNA于缺血再灌流12～24h达高峰,2～4d呈降低趋势,至16d略高于假手术组.结论脑缺血再灌流后细胞凋亡介导神经细胞损伤、坏死是一个渐进的动态演变过程.Bcl-2蛋白、Caspase-3mRNA表达在抑制细胞凋亡和介导神经细胞损伤等方面起非常重要的作用.

简介：目的研究ＴＮＦ－α对胶质瘤细胞的抑制作用及其对Ｂｃｌ－２蛋白表达的影响。方法应用细胞计数法和ＭＴＴ法研究经ＴＮＦ－α处理的大鼠Ｃ６胶质瘤细胞的生长和增殖活性，研究了细胞的形态学变化及及用免疫细胞化学方法检测ＰＣＮＡ（增殖细胞核抗原）和Ｂｃｌ－２蛋白表达。结果ＴＮＦ－α对体外培养Ｃ６胶质瘤细胞生长和增殖具有呈时间和剂量依赖性的抑制作用，下调ＰＣＮＡ的表达，并诱导细胞凋亡，但对抑调亡蛋白Ｂｃｌ－

简介：目的比较缺血后适应与缺血再灌注（IR）条件下海马组织内抗凋亡通路JAK2-STAT3-BCL2的表达及激活情况,并比较两种条件下的小鼠海马组织细胞凋亡及认知水平,同时在抑制JAK2、STAT3的条件下观察其对缺血后适应的脑保护作用的影响。方法用水迷宫试验比较两组小鼠认知功能差异;用Westernblot方法测定相关蛋白的表达;用TUNEL染色比较细胞凋亡水平;用特异性抑制剂WP1066观察在JAK2、STAT3受抑制的条件下缺血后适应的脑保护效果。结果在缺血后适应的条件下小鼠海马组织中JAK2-STAT3-BCL2通路被明显激活。缺血后适应组JAK2、STAT3、p-JAK2、p-STAT3、BCL2表达均升高（均P〈0.05）,海马组织细胞的凋亡程度明显减轻,凋亡细胞数明显较IR组降低（P〈0.01）,凋亡相关蛋白及caspase-3、Bax表达明显降低（均P〈0.05）。认知功能损害程度指标（隐藏平台实验与空间探索实验）水迷宫逃避潜伏期以及进入靶象限占比与IR组相比差异有统计学意义（P〈0.01,P〈0.05）。在抑制JAK2、STAT3的条件下缺血后适应的认知保护作用下降,水迷宫逃避潜伏期以及进入靶象限占比与缺血后适应组相比差异有统计学意义（均P〈0.05）,细胞凋亡数增多（P〈0.05）,JAK2、STAT3、p-JAK2、p-STAT3、BCL2表达下降,而凋亡相关蛋白caspase-3、Bax表达上升（均P〈0.05）。结论缺血后适应通过激活JAK2-STAT3-BCL2通路,抑制IR损伤海马组织细胞的凋亡,保护认知功能,继而发挥内源性脑保护作用。

简介：目的探讨MMP-2和TIMP-2与胶质瘤侵袭性及恶性表型之间的关系及其意义.方法采用Elivision二步免疫组织化学法染色观察MMP-2和TIMP-2在46例不同恶性度胶质瘤及10例正常脑组织中的表达并用德国LeicaQ550cw图像分析系统测其灰度值作为表达强度的量化指标.结果在对照组、低度及高度恶性胶质瘤中,MMP-2的阳性表达率分别为10%、63.6%和95.8%;在对照组、低度及高度恶性胶质瘤中,TIMP-2的阳性表达率分别为10%、36.3%和37.5%.MMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为173.27±13.26和98.63±18.20;TIMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为210.44±12.95和205.65±9.75.结论MMP-2表达随胶质瘤恶性程度增加而增强,可作为胶质瘤恶性表型及侵袭性指标之一.TIMP-2表达在正常脑组织及不同级别胶质瘤中无明显差异.MMP-2/TIMP-2的比值与胶质瘤侵袭性密切相关.

简介：RolesofKeap1-Nrf2pathwayinbrain:NeuronalsurvivalandneurogenesisareimpairedinneurodegenerativediseasessuchasParkinson’sdiseaseandAlzheimer’sdisease(Winneretal.,2011).Geneticup-regulationofgrowthfactorsenhancedneuronalsurvivalandneurogenesis,improvedneuronalfunctionsandhalteddiseaseprogressioninanimalmodelsofAlzheimer’sdisease

简介：BACKGROUND:Mailuoning,aChineseherb,hasbeenwidelyusedinChinatotreatacuteischemicstroke,andthemajorcomponentexhibitsanti-oxidativeeffects.However,thepreciseanti-oxidationpathwayremainsuncertain.OBJECTIVE:TovalidatetheprotectiveeffectsofMailuoningonH2O2-inducedprimarycorticalneuroninjuryinembryonicmice.DESIGN,TIMEANDSETTING:ComparativeobservationandinvitroexperimentswereperformedattheJiangsuKeyLaboratoryforMolecularMedicinefromJanuary2008toSeptember2009.MATERIALS:Mailuoning(NanjingJinlingMedicalCompany,China),reactiveoxygenspecies(ROS)kit(BeyotimeBiotechnology,China),superoxidedismutase(SOD),Cu/ZnSODkit,malondialdehyde(MDA)kits(NanjingJiancheng,China),mitochondrialmembranepotential(GMS10013.1,GENMED,USA)andcatalaseactivityassaykit(BeyotimeBiotechnology,China)wereutilizedforthepresentstudy.METHODS:MouseembryoniccorticalneuronswereisolatedandculturedwithculturemediumcontainingH2O2(80μmol/L)and/orMailuoning(1.25μg/mL)for24hours.MAINOUTCOMEMEASURES:Neuronalviabilityanddeathweredetectedbymethylthiazolyltetrazdiumandflowcytometry;ROSproductionwasdeterminedbyflowcytometry;mitochondrialmembranepotentialwasdetectedusingfluorescentstaining;SODactivitywasdetectedusingamodifiednitrobluetetrazoliummethod;Cu/ZnSODandcatalaseactivitywasdetectedbyspectrophotometry;andMDAwasdeterminedusingthelipidperoxidationmethod.RESULTS:H2O2increasedROSproductionandMDAconcentration(P<0.05),anddecreasedmitochondrialmembranepotential,SOD,Cu/ZnSODandcatalaseactivity(P<0.05);thenumberofsurvivingneurons(P<0.05)wasalsoreduced.Mailuoningreversedthesechanges.CONCLUSION:MailuoningprotectsH2O2-inducedinjuryincorticalcellsbyinhibitingROSandMDA,increasingdepolarizationofmitochondrialmembrane,andenhancingSODandcatalaseactivity.

简介：目的总结椎管内巨大脂肪瘤的诊治经验。方法回顾性分析2例椎管内巨大脂肪瘤病人的临床资料,采用后正中入路行椎管内肿瘤切除术。结果2例肿瘤次全切,病理检查均为脂肪瘤。术后1个月、3个月进行随访,病人恢复良好。结论椎管内脂肪瘤手术全切难度较大,以脊髓减压为目的行次全切手术可收获良好的短期预后。

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简介：目的研究刺五加多糖（ASPS）对H2O2诱导的海马神经元凋亡的影响及其机制。方法采用H2O2诱导大鼠海马神经元凋亡。采用末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法检测细胞凋亡率、免疫组化法检测caspase-3蛋白的表达、逆转录PCR法检测caspase-3mRNA的表达。结果H2O2作用后,海马神经元凋亡率、caspase-3蛋白和mRNA表达水平均显著增高（P〈0.05）;给予ASPS干预后,均显著下降（P〈0.05）;而且,随ASPS剂量增加,作用效果显著增强（P〈0.05）。结论ASPS具有抑制氧化应激损伤诱导神经细胞凋亡作用,其机制与下调caspase-3mRNA的表达有关。

简介：Thismini-reviewpresentstheauthors'visiononthecurrentstatusandfuturetrendsinthedevelopmentofneuroprotectiveagentsworkingviaactivationofnuclearfactorerythroid2-relatedfactor2(Nrf2),andinparticular,viadisruptionofNrf2-Keaplinteraction.Therearetwoopposite'chemical'mechanismsunderlyingsuchactivation:thefirstoneisanon-specificcovalentmodificationofKeap1thiols,resultinginsideeffectsofvariedseverity,andthesecondoneistheshiftoftheNrf2-Kelch-likeECHassociatedprotein-1(Keap1)bindingequilibriuminthepresenceofacompetitiveandchemicallybenigndisplacementagent.Atthispoint,nodisplacementactivatorsexhibitsufficientbiologicalactivityincomparisonwithcommonNrf2activatorsworkingviaKeaplthiolmodification.Hence,thehopeintherapeuticsisnowlinkedtotheFDAapproveddimethylfumarate,whosederivative,monomethylfumarate,aswedemonstratedrecently,ismuchlesstoxicbutequallybiologicallypotentandanidealcandidateforclinicaltrialsrightnow.AnewlyemergingplayerisanuclearinhibitorofNrf2,BTBdomainandCNChomolog1(Bach1).ThecommerciallydevelopedBachlinhibitorsarecurrentlyunderinvestigationinourlaboratoryshowingpromisingresults.Inourviewpoint,theperfectfuturedrugwillpresentthecombinationofadisplacementactivatorandBachlinhibitortoinsuresafetyandefficiencyofNrf2activation.

简介：颅内原发性生殖细胞瘤好发于松果体区,而发生于基底节区较少见,临床上常诊断为基底节胶质瘤.该肿瘤多发生于儿童,早期诊断较为困难.近年来我科收治2例基底节区生殖细胞瘤,经治疗后效果满意.现报告如下.

简介：苯妥英(PHT)为临床上最常用的第一线抗癫痫药,但个体间对PHT代谢呈现较大差异.目前证实细胞色素氧化酶P450(CYP)2C9/19是体内参与PHT羟化的主要代谢酶.人群CYP2C9/19遗传基因呈多态性,从而引起对PHT代谢个体间较大差异,部分人群对PHT呈强代谢(EM),另一部分人群呈弱代谢(PM),了解这些知识对临床用药十分重要.本文试对该方面内容进行综述.

简介：由王保国教授和周建新教授主编的《实用呼吸机治疗学》（第2版）已于2005年10月由人民卫生出版社出版。