乌灵胶囊增加慢性不可预见性温和应激大鼠海马连接蛋白43的表达改善神经再生

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1、乌灵胶囊增加慢性不可预见性温和应激大鼠海马连接蛋白43的表达改善神经再生作者：李德强,李旭娟,段金凤,蔡巍【摘要】　　　　目的：探讨乌灵胶囊对慢性不可预见性温和应激(chronicunpredictablemildstress,CMS)抑郁模型大鼠海马齿状回脑源性神经营养因子(brainderivedneurotrophicfactor,BDNF)、神经再生，以及连接蛋白43(connexin43,Cx43)表达的影响。方法：45只成年雄性SpragueDawley大鼠随机分入对照组(n=15)、模型组(n=15)和乌灵胶

2、囊组(n=15)。模型组和乌灵胶囊组大鼠接受连续3周的CMS，造模期间，乌灵胶囊按100mg/(kg·d)加入乌灵胶囊组大鼠的膳食中，连续治疗21d。采用糖水偏爱实验评价大鼠的抑郁程度。抑郁行为测试结束后，取双侧海马组织，用免疫组织化学法检测BDNF与5溴脱氧尿苷(5bromodeoxyuridine，BrdU)的表达；用逆转录聚合酶链反应和蛋白印迹法检测海马中Cx43mRNA与蛋白表达。结果：慢性应激大鼠齿状回BDNF阳性表达、新生细胞数及Cx43mRNA和蛋白表达水平均较正常大鼠明显下降。乌灵胶囊治疗后，CMS大鼠抑郁

3、行为得到改善，异常的海马神经再生恢复，Cx43mRNA和蛋白表达变得正常，但BDNF表达无明显改变。结论：乌灵胶囊可增加CMS模型大鼠海马神经再生及改善抑郁症状，其机制可能与增加Cx43表达有关，与BDNF无关。24【关键词】慢性不可预见性温和应激;脑源性神经营养因子;5溴脱氧尿苷;连接蛋白;大鼠　　Recently,greatprogresseshavebeenmadeinunderstandingthepathogenesisofdepression,suchasthecreationofthechronicunpred

4、ictablemildstress(CMS)model［1］andthehypothesisthathippocampalbrainderivedneurotrophicfactor(BDNF)downregulationanddysfunctionalneurogenesismayleadtothedepressedbehaviors［2］.Substantialresearchevidenceindicatedthatstressplaysanimportantroleinthepathogenesisofdepres

5、sion［3］,butitsmechanismstillneedstobeexactlyelucidated,especiallyinmakingclearwhatsubstratesareinvolvedandhowthesepertinentsubstratesmediatestressinducedinhibitionofhippocampalneurogenesis.Thistopichascurrentlycausedmoreattentionandhasbecomeanewhotspot［4］todeeplyex

6、plore.Invitroandinvivoexperimentalevidencesuggeststhatgapjunctions,formedbyconnexins(Cxs)betweenneuronsand/orastrocytes,contributetotheneuralgenerationandrecoveryafterlesion［5］.Cx43,asaspecificconnexin,ismainlylocatedinastrocytesandisknowntoparticipateinvariousdevel

7、opmentalstagesofcellproliferation,includingneuronalmigration,axonal24elongation,axonpruning,dendritemorphogenesisandsynapticmaturation.However,therelationshipbetweenCx43expressioninhippocampusandabnormalneurogenesisinducedbyCMSisstillunclearsofar.WulingCapsule,acomp

8、oundtraditionalChineseherbalmedicine,hasbeenusedinclinicformanyyears,andhasbeenprovedtobepotenttofullyimprovethesignsofinsomniaandcognitiv