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1、新生大鼠缺氧缺血腦損傷時腦組織STAT3信號通路的作用鄧睿1周立剛1趙鳳艷2張莉2李德淵2母得志2(400013重慶,重慶市婦幼保健院新生兒科;610041四川成都,四川大學華西第二醫(yī)院兒科2)[摘要]目的研究信號轉導和轉錄激活因子3(STAT3)信號通路在新生大鼠缺氧缺血(HI)腦損傷中的作用。方法采用Rice法建立7日齡SD大鼠缺氧缺血腦損傷(HIBD)模型,同時設立對照。于HI后4h、6h、8h、12h和24h取腦,采用免疫組織化學法及Westernblot檢測STAT3、磷酸化STAT3(p-STAT3)及血管內
2、皮生長因子(VEGF)的表達與分布,TUNEL法檢測神經細胞凋亡。結果HI組p-STAT3蛋白表達在HI后4h升高,6h達高峰,8~12h逐漸下降,均明顯高于假手術組,差異有統(tǒng)計學意義(P﹤0.05)。而STAT3總蛋白表達與假手術組比較,差異無統(tǒng)計學意義(P﹥0.05)。VEGF于HI后各時間點均明顯高于假手術組,差異有統(tǒng)計學意義(P﹤0.05)。TUNEL染色陽性細胞數于HI后24h達高峰,明顯高于假手術組,差異有統(tǒng)計學意義(P﹤0.01)。結論新生大鼠HI后,p-STAT3蛋白表達增高,可能誘導VEGF表達,對神經
3、元的凋亡具有抑制作用。[關鍵詞]信號轉導和轉錄激活因子;STAT3;血管內皮生長因子;凋亡;缺氧缺血性腦損傷;新生大鼠[中圖分類號]R-72[文獻標識碼]A[文章編號]ThefunctionofSTAT3signalingpathwayinneonatalratsfollowinghypoxic-ischemiabraindamageAbstract:ObjectiveToinvestigatethefunctionofSTAT3signalingpathwayinneonatalratsunderhypoxiaisch
4、emia(HI)condition.MethodsHypoxic-ischemiabraininjuryanimalmodelwasmadeusing7-day-oldSDratsaccordingtoRice-Vannuccimodel,andcomparativestudiesweremadewithashamgroup.Braintissueswerecollectedafter4h、6h、8h、12hand24hofrecoveryfromHI.Immunohistochemistryandwesternblot
5、wereusedtodetecttheexpressionanddistributionofSTAT3,phosphorylatedSTAT3(p-STAT3)andvascularendothelialgrowthfactor(VEGF);cellapoptosiswasdetectedbyTdT-mediateddUTP-biotinnickendlabeling(TUNEL)staining.ResultsIntheHIgroup,Thep-STAT3proteinsignificantlyincreasedat4
6、hours,reachedthepeakat6hours,begantodecreaseat8-12hours,whichweresignificanthigherthanthoseintheshamgroup(P﹤0.05).TherewasnosignificantdifferenceobservedwhencomparedtheexpressionoftotalSTAT3proteinintheHIgroupwiththoseoftheshamgroup.IntheHIgroup,theVEGFexpression
7、washigherthanthatintheshamgroupateachtimepoint.TUNELstainingshowedthatthepositivecellspeakedat24hours,andthepositivecellsweresignificantlymorethanthoseofshamgroup(P﹤0.01).ConclusionThep-STAT3proteinexpressionwassignificantlyincreasedafterHI,p-STAT3mayinduceVEGFex
8、pression,andinhibitneuronalapoptosisafterHI.Keywords:Signaltransducerandactivatoroftranscription;STAT3;VascularendothelialGrowthfactor;Apoptosis;Hypoxic-ischem