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Protective effect of β-asarone on PC12 cells injury induced by Aβ1-42 astrocytic activation

β-细辛醚对Aβ1-42诱导星形胶质细胞活化所致PC12细胞损伤的保护作用研究



全 文 :2016
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Vol41,No.7 April,2016

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,Tel:(0571)86613537,Email:lm159@sinacom

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βZ[Cì Aβ142\]^_`ÞZað_
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|^4ÚβZ[CìAβ142\]^_`ÞZað_bcPC12Zaƒ„±de0žÊÓfË,•βZ[C¿KLM
HNO
(Alzheimer’sdiease,AD)
2±‚ž#G烷> 。 HQ , pžçOr¨¶ßZa—à() (Realtimecelanaly sis,RTCA) ÷€ RAh/PC12 ”4½°Å , çO¶ß¤ Aβ142\]^_`ÞZaƒ„Yì”4½°Å$PC12Zað‡±ò ó , Ø>Åƕ¶Â–±ð‡.›¬Ý=;dQ­±,˜jkOþ , pž¥¦Å¾± βZ[Cì^_`ÞZaÖnjk, ¤”4½°Å$ PC12 Zað‡±T  ; Óº , pž MTT ‚á Aβ1420žŸRAhìPC12Zað‡±òóaÊ βZ [C±jkɂ , ƒŠ RTCA ±‚áœæ ; Ö[Ípž ELISA ‚á@„4½¤$ IL1β,TNFα,BDNF±¢%;Westernblot ‚á PC12 Za NFκB±ðµ¬ERK,p38,JNK5¼_¢%。œæhi,βZ[C(555mg·L-1){h·&y Aβ142\]± RAh ð_Íá± PC12 Zað‡@ä (P<001), h·ät@„4½¤$ IL1β,TNFα±¢%¬ PC12Za ERK,p38,JNK 5¼_¢% (P<001);βZ[C(1667mg·L-1){Ö@„4½¤$BDNF±Ï;(P<005)。a÷œæ*ú,Aβ142\] RAh ð_¬Ï; IL1β,TNFαè0ÝàïÅÛ PC12Za±ƒ„;βZ[C{ät IL1β,TNFα¬Ö BDNF±Ï;,9Ë PC12 Za NFκB±ðµ¬ERK,p38,JNK5¼_¢%。 [ œž ] βZ[C;Aβ142;^ _`ÞZa;PC12Za;RTCA;NFκB ProtectiveefectofβasaroneonPC12celsinjuryinducedby Aβ142astrocyticactivation HEYing,HEJiana,FUJun,BAOYuting,LIChangyu,YANGYuanxiao (ColegeofPharmaceuticalScience,ZhejiangChineseMedicalUniversity,Hangzhou310053,China) [Abstract] ThisstudywasaimedtoinvestigatetheprotectiveefectandmechanismofβasaroneonPC12celsinjuryinduced byAβ142activatedastrocytes,andprovideexperimentalbasisforβasaroneapplicationinthepreventionandcontrolofAlzheimer′sdis ease(AD)Firstly,RAhandPC12celswerecoculturedinthespecialtranswelchamber,andtheRealtimecelanalysis(RTCA) systemwasusedtorealtimeobserveitsefectonPC12celssurvivalrateinthecoculturesystemafterastrocytesinjuryinducedby Aβ142.Thebestinterventiontimeofβasaronewasselectedaccordingtothesurvivalcurveandparametersgeneratedautomaticaly βasaronewithdiferentconcentrationswasusedforinterventiononastrocytes,thenthechangesofPC12celssurvivalrateintheco culturesystemwereobservedSecondly,MTTassaywasusedtodetecttheefectofAβ142onPC12celssurvivalrateaswelasthein terventionefectofβasarone,andverifythetestingresultsofRTCAThelevelsofIL1β,TNFαandBDNFinculturemediaofthe lowerchamberweredetectedbyELISATheNFκBactivityandphosphorylationlevelsofERK,p38andJNKweredetectedbyWest ernblotResultsshowedthatβasarone(555mg·L-1)couldsignificantlyslowdownthedeclineofPC12celssurvivalratecaused byAβ142inducedRAhactivation(P<001),significantlyreducethelevelsofIL1β,TNFαandthephosphorylationlevelsofERK, ·2821· f  Ùè :βZ[CìAβ142\]^_`ÞZað_bcPC12Zaƒ„±de0ž«¬ p38andJNKinculturemediaofthelowerchamber(P<001)βasarone(1667mg·L-1)couldpromotethereleaseofBDNFin culturemediaofthelowerchamber(P<005)TheseresultsindicatedthatAβ142couldinduceRAhactivationanditsreleaseofIL 1β,TNFαandotherinflammatoryfactorstoaggravatethePC12celsinjury;βasaronecouldreducethelevelsofIL1β,TNFα,pro motethereleaseofBDNF,andinhibittheNFκBactivityaswelasphosphorylationlevelsofERK,p38andJNKproteininPC12cels [Keywords] βasarone;Aβ142;astrocyte;PC12cel;RTCA;NFκB doi:10.4268/cjcmm20160720    ÎyÏ«¬m± ,^ _`ÞZa0•$žŒ ÅÆQjw±Zaÿ , ÑKLMHNO (Alzheimer′s diease,AD) ±mÂm×cd€ 。AD ó}Md± ÓÔ 、 +,±^_`ÞZaˆð [1], Óm׸¹$ v8츿Ña^_`ÞZaˆð•–+±0Ý Ö‚ 。 ˆð±^_`ÞZaã¬Ï;…ß0Ýà ﬌¼½àïè , áÌMÖn•¿de , Aæ㠃F , deŒ~ , +,±0Ýւ{ÅÛ Aβ± Â– , ÅöŒ~±ƒ„ , \m AD[2]。 9çƒ@¸ ÷€^_`ÞZa¬ PC12 Za±”4½°Å0•« ¬ì- , {„÷FPav8ÓM² , òýŸ°ð«¬ ŒÅÆÜO±U[ZaPQ-B[â±½ß 。 ›¤¥•Ë9^&Ž˜›¤¥ Acorustatari nowiSchot ±j©Ø@ , -BIÚr… 、 ی±Õ ±¥É , …†÷ÓԂžŸÜÝ 、 »¯ 、 —• 、 $ÇV V 、 õyµÀÁèOÝ [3]。βZ[C•›¤¥±L /Bɖ— , Óì βIã#|}\]± PC12Za ë/-B9Ë0ž [45], ì AD PQ…RHRŒ~ ë/B[â±de0ž [67]。 9“í}«¬m ± ,βZ[CìAβ142\]ð_±^_`ÞZaƒ„ Bde0ž 。 }βZ[C±0žÑAβð_±^_ `ÞZaì PC12 Za±òó3b]kÚ 。 9^¿ í}烱1i÷ , «¬ βZ[Cì Aβ142\]^ _`ÞZað_bc PC12 Zaƒ„±de0ž , •βZ[C¿AD2±‚ž#G烷>。
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Vol41,No.7 April,2016
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·5821·
2016
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41
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Vol41,No.7 April,2016
t
(P<001);βZ[C(555mg·L-1)PC12Z
að‡€ñŸ
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Q@„4½¤ IL1β,TNFα,BDNF¢%uh· ÜÝ (P<005 p P<001); Ñ Aβ142PQ€ñ, βZ[C(185,555mg·L-1) IL1β,TNFα¢ %uh·ät (P<005 p P<001),βZ[C (1667mg·L-1) IL1β,TNFα¢%rh· _; ïð ,βZ[C(1667mg·L-1){ÖBDNF± Ï; (P<005), ]* 1。 35 βZ[CìPC12ZaNFκBðµ±òó NFκBL/¥{µð1p56¿Za±âíÖ
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Q
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1 βZ[Cì”4½°Å@„Zaàï¢%±òó
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IL1β
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555 3706±0624) 2294±6864) 8512±151
185 3836±3553) 2511±5334) 8665±286
  
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œæm±βZ[C(555mg·L-1){BÉ
ät”4½@„ IL1β,TNFα¢%。Kimuraè« ¬m± , ¿ AD ó}Mm±^_`ÞZaì Aβ±Ö ‚µøe ,AβM\]^_`ÞZaãÂv>µŒ ¼½àï (BDNF), ֌~ƒ„Y±ð¬A æ [1214], &t AβbcŒhµ。9烫¬m±, βZ[C(1667mg·L-1){Ö BDNF±Ï;。 ×]0ÝQL/±@N• NFκB@N,AD±m fËÑÓopàï±ðµ˜Ïcd€ , +,±0 ݬt_‚ˆèÍá± NFκB¸¾ˆð+ÅÛ0 ·7821· 2016 y 4 z ³ 41 ų 7 } Vol41,No.7 April,2016 Ýւ¬t_‚ˆ , ֌~±ë/ ; [[Ò×] 0ݱL/v<@NÉ MAPK @N , RSZaðv <˜Ï|}ˆq (extracelularsignalregulatedki nase,ERK),cJun ¡1幈q (cjunNH2termi nalkinase,JNK) ¬ p38 ÑÝrð_|}ˆq (p38 mitogenactivatedproteinkinase,p38), [² MAPK G 5¼_§ˆð , ‰MaÖ[Í5¼_¬ˆðÓ∠qpopàï , › NFκB¬ AP1è[15]。9“ í}烜æ*ú ,βZ[C{9Ë^_`ÞZa p38,ERK ±5¼_¢%è 。 9烫¬m± , βZ[C(555mg·L-1){BÉ9Ë@„ PC12Z a± NFκBðµ¬ERK,JNK±5¼_¢%。 ‰÷bg ,βZ[CM{@¸Ö BDNF±Ï ; , ät IL1β,TNFα±¢%¬ERK,JNK±5¼_ ¢% , aÊ9Ë PC12 Za NFκBðµ§áäde 0ž 。 [ „q= ] [1] CarterSF,ScholM,AlmkvistO,etal.Evidenceforastrocytosis inprodromalAlzheimerdiseaseprovidedby11CdeuteriumLde prenyl:amultitracerPETparadigm combining11Cpitsburgh compoundBand18FFDG[J].JNuclMed,2012,53(1):37. [2] HoozemansJJ,RozemulerAJ,vanHaastertES,etal.Neuroin flammationinAlzheimer′sdiseasewaneswithage[J].JNeu roinflam,2011,8:171. [3]  ŸÛ , œlè .βZ[C¿…R°8±,P¶ñ[J]., k ,2004,39(10):836. [4] LiCC,XingGH,DongMX,etal.Betaasaroneprotection againsebetaamyloidinducedneurotoxicityinPC12celsviaJNK signalingandmodulationofBcl2familyproteins[J].EurJ Pharmacol,2010,635(1/3):96. [5] ZouDJ,WangG,LiuJC,etal.Betaasaroneatenuatesbeta amyloidinducedapoptosisthroughtheinhibitionoftheactivation ofapoptosissignalregulatingkinase1inSHSY5Ycels[J]. Pharmazie,2011,66(1):44. [6] GengYT,LiCC,LiuJC,etal.Betaasaroneimprovescognitive functionbysuppressingneuronalapoptosisinthebetaamyloid hippocampusinjectionrats[J].BiolPharmBul,2010,33(5): 836. [7] LiuJC,LiCC,XingGH,etal.Betaasaroneatenuatesneuro nalapoptosisinducedbybetaamyloidinrathippocampus[J]. YakugakuZasshi,2010,130(5):737. [8] SharmaG,VijayaraghavanS.Nicotiniccholinergicsinalingin hippocampalastrocytesinvolvescalciuminducedcaliumrelease fromintracelularstores[J].ProcNatlAcadSci,2001,98:4148. [9] LanhaiLü,YingTMak,MarongFang,etal.Thediferencein gliosisinducedbyβamyloidandTautreaurentsinastrocytecul turesderivedfrom senescenceacceleratedandnormalmouse strains[J].Biogerontology,2009,10(6):695. [10] ShibataM,YamadaS,KumarSR,etal.ClearanceofAlzheimer′ samyloidss(140)peptidefrombrainbyLDLreceptorrelated protein1atthebloodbrainbarier[J].ClinInvest,2000,106 (12):1489. [11] TanZS,BeiserAS,VasanRS,etal.Inflammatorymarkers andtheriskofAlzheimerdisease[J].Neurology,2007,68(22): 1902. [12] KimuraN,TakahashiM,TashiroT,eta1.Amyloidbetaupreg ulatesbrainderivedneurotrophicfactorproductionfrom astro cytes:rescuefromamyloidhetarelatedneuriticdegeneration[J].J NeurosciRes,2006,84(4):782. [13]  B™ö , y–û , yíV , è . v>µŒ¼½àï¿ïµé ꃄYŒAæ0ž±«¬Ö×
[J].
é”ð&-.

2010,8(4):250.
[14] 
!ë<

p:^

—Œ

v>µŒÂËàï9˃ˆ¡¼
\]±Œ~ë/
[J].
…†ü&-.
,2008,26(12):1067.
[15] HommesDW,PeppelenboschMP,DeventerSJH.Mitogen
activatedprotein(MAP)kinasesignaltransductionpathwaysand
novelantiinflammatroytargets[J].Gut,2003,52(1):144.

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