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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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] 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·
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: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
  
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·5821·
2016
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41
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Vol41,No.7 April,2016
t
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að‡€ñŸ
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‚
NFκB±ðµ。Westernblotœæhi,Aβ142P
Q
NFκBp56*sh·ÝŸ?wìH(P<
001);βZ[C(555,1667mg·L-1)òý
Aβ142PQNFκBp56*sh·ät(P<001),
βZ[C(185mg·L-1)Ñ Aβ142PQ€ñ,
NFκBp56*sßrh· _,]q4。
*
1 βZ[Cì”4½°Å@„Zaàï¢%±òó
Table1 Efectofβasaroneonlevelofcytokinesfromthelower
chamberinthecoculturesystem
`
Ãß
/mg·L-1
IL1β
/ng·L-1
TNFα
/ng·L-1
BDNF
/ng·L-1
?w
- 3548±302 2570±189 5895±365
PQ
- 4609±0991) 2984±1512) 8570±4182)
βZ[C 1667 3892±480 2830±743 9293±5463)
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
  
å

Ñ?wìH€ñ
1)P<005,2)P<001;
Ñ
Aβ142PQ
ۖ
3)P<005,4)P<001。
A
?w
;BAβ142PQ;CβZ[C(185mg·L-1);DβZ
[C
(555mg·L-1)

;EβZ[C(1667mg·L-1)(q5¦)。
q
4 βZ[CìPC12ZaNFκBðµ±òó
Fig4 EfectofβasaroneonNFκBp65expressioninnucleus
ofPC12cel
·6821·
f 
Ùè
:βZ[CìAβ142\]^_`ÞZað_bcPC12Zaƒ„±de0ž«¬
36 βZ[Cì PC12Za ERK,p38,JNK5¼_
¢%±òó
Westernblot
Ͼhi
,Aβ142PQ± ERK,
p38,JNK
5¼_¢%uh·ÝŸ?wìH
(P<
001);βZ[C(185,555,1667mg·L-1)
ERK
±5¼_¢%€ñŸ
Aβ142PQuh·ät
(P<001);p38
±5¼_¢%€ñŸ
Aβ142PQ
urh·òó

Ñ
Aβ142PQ€ñ,βZ[C
(555,1667mg·L-1)
{h·ät
JNK
±5¼_
¢%
(P<001),βZ[C(185mg·L-1)ì JNK
±5¼_¢%rh·òó

]q
5。
q
5 βZ[Cì PC12Za pERK,pp38,pJNKðµ±
òó
Fig5 EfectofβasaroneonpERK,pp38,pJNKexpression
inPC12cel
4 
Ús
›¤¥ÉÓԂžŸ$žŒÅÆÜO$ˆ±
$,

-BŒ~de

Tٜ¨è0ž
。βZ
[C•›¤¥±L/𵖗ý[

¿°8©ª—
‹D

åt@¸¢v´D

9“í}«¬m
±
,βZ[Cì5¦§¾bc±œ¨;ìð¬¼Ìbc±¨>DŸÊm¨bc±¨
W±DŸPQ:RuBTÙ¨±0ž

ì
Aβ2535
bc±
PC12
Zaƒ„Bôë/0ž

ì
Aβ142\]
^_`ÞZað_bc±ƒ„Bde0ž

hid
Õ÷±«¬íÊ

^_`ÞZa0•$žŒÅÆ8—‹QÓ±
Za

ь~ýþ¿æ-±€ß0ž

ӈð×
]±ŒÅÆ0Ýւ¿Œ(nµÜO±mO¬
m׸¹$áÑ./±0ž
8]。
«¬m±
[9]AD
û
üv$¿…߈ð±^_`ÞZa

Cf¿Œ
0µæ…,C
。AβMaÍá^_`ÞZa±ð_,
ð_±^_`ÞZa$ëB
Aβ-¨,•Ó¿Aβ±
ä7$mˆ0ž

’“œæu*ú^_`ÞZa¿
AD
$mˆ./0ž

H¾ˆð±^_`ÞZaM

Aβ|},Ï;Œ¼½àï,deŒ~;}
¸¾ˆð±^_`ÞZa

@¸Ï;Œhµ±Z
aàï¬Óâhµ˜Þ

\]Œ~ë/

Åö
AD
OSÖ¹

9çƒ@¸÷€^_`ÞZa¬
PC12
Za±
”4½°Å

Ž÷FPav8ÓM²¬

Za€
ß0ž±Å

¶ βZ[C0žŸ Aβ142ð_±
RAh
Za

¤ÑӔ4½±
PC12
Zað‡±
 _

œæm±
,10μmol·L-1Aβ1420ž24,48h
u{I
PC12
Za±ð‡h·@ä
,βZ[C
(555mg·L-1)
{h·#Ý
PC12
Za±ð‡

βZ[C{BÉF9ËAβ142\]RAhð_]c±
PC12
Zað‡@ä

de
PC12
Za

烦9Ë0ݾ¾

«¬ βZ[Cmˆde
0ž±ÌÍfË
。AβãK°0žŸ^_`ÞZa,
MI^_`ÞZaÏ;…ß0Ýàï

›
IL1β,IL
6,TNFα,IL8,ðµtè,0•Ì챘Q0ÝÖ
‚

’“˜Þ쌍~Bhµ0ž

IŒ~ë
/
[1011]。
í}烫¬m± βZ[C{9Ë Aβ142
ð_±^_`ÞZa
IL1β,TNFα±*s。9çƒ
pž¥¦Å¾± βZ[CS Aβ142ð_±^_`
ÞZa

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±mÂ
fËÑÓopàï±ðµ˜Ïcd€

+,±0
ݬt_‚ˆèÍá±
NFκB¸¾ˆð+ÅÛ0
·7821·
2016
y

z ³
41
ų

}
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),

MAPK
G
5¼_§ˆð

‰MaÖ[Í5¼_¬ˆðÓâˆ
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

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



„q=

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‘’“

·8821·