17-91 Dl-3-n-butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4NF-κB signalling.

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1、J.Cell.Mol.Med.VolXX,NoX,2017pp.1-13Dl-3-n-butylphthalideattenuatesacuteinflammatoryactivationinratswithspinalcordinjurybyinhibitingmicroglialTLR4/NF-jBsignallinga,b,#a,b,#bacbZiliHe,YulongZhou,LiLin,QingqingWang,SinanKhor,YuqinMao,JiaweiaaabdebLi,ZengmingZhen,JianChen,ZhenzhenGao,FenzanW

2、u,XieZhang,HongyuZhang,ab,a,b,Hua-ZiXu,ZhouguangWang*,JianXiao*aDepartmentofOrthopaedics,TheSecondAffiliatedHospitalandYuyingChildren’sHospitalofWenzhouMedicalUniversity,WenzhouMedicalUniversity,Wenzhou,Zhejiang,ChinabMolecularPharmacologyResearchCenter,SchoolofPharmaceuticalScience,Wenzh

3、ouMedicalUniversity,Wenzhou,Zhejiang,ChinacDepartmentofMolecularPharmacology,AlbertEinsteinCollegeofMedicine,Bronx,NY,USAdDepartmentofNeurosurgery,AffiliatedCixiPeople’sHospital,WenzhouMedicalUniversity,Ningbo,ChinaeDepartmentofGastroenterology,NingboMedicalTreatmentCenterLiHui-liHospital

4、,Ningbo,Zhejiang,ChinaReceived:October19,2016;Accepted:March28,2017AbstractInthisstudy,weexaminedtheneuroprotectiveeffectsandanti-inflammatorypropertiesofDl-3-n-butylphthalide(NBP)inSprague-Dawley(SD)ratsfollowingtraumaticspinalcordinjury(SCI)aswellasmicrogliaactivationandinflammatoryrespo

5、nsebothinvivoandinvitro.OurresultsshowedthatNBPimprovedthelocomotorrecoveryofSDratsafterSCIansignificantlydiminishedthelesioncavityareaofthespinalcord,apoptoticactivityinneurons,andthenumberofTUNEL-positivecellsat7dayspost-injury.NBPinhibitedactivationofmicroglia,diminishedthereleaseofinfl

6、ammatorymediators,andreducedtheupregulationofmicroglialTLR4/NF-jBexpressionat1daypost-injury.Inaco-culturesystemwithBV-2cellsandPC12cells,NBPsignificantlyreducedthecytotoxicityofBV-2cellsfollowinglipopolysaccharide(LPS)stimulation.Inaddition,NBPreducedtheactivationofBV-2cells,diminishedth

7、ereleaseofinflammatorymediators,andinhibitedmicroglialTLR4/NF-jBexpressioninBV-2cells.OurfindingsdemonstratethatNBPmayhaveneuroprotectiveandanti-inflammatorypropertiesinthetreatmentofSCIbyinhibitingtheactivationofmicrogliaviaTLR4/NF-jBsignalling.Keywords:Dl-3-n-butylphthalid