全 文 :2016
y
3
z ©
41
ª©
5
}
Vol41,No.5 March,2016
O~l$mBScOPÉÊ°ÂËÌ
noÉÊpq
Ø*Æ
,
7+
,
QRM
,
,.v
,
-±
,
-
(
hi?¨ X¨õ Z¨Y fZ©njéZ©@`abcde
,
hi
100191)
[
op
]
O~lɯ¼E>ʤFS?BÆr)fBÏÒ-
,
Ì,W.£»ÉÊfôRÌkdï
^
。
¯¿.CO~l°Â.£»ËÌÉÊfô
,
µ^ÉÊ^gÔZ
/
ð^
(OGD/R)
·v
H9c2
Sc¿j¬K
Ø
,
±O~lËÌø,#ö_ñ.¼nScOP°ÂLM
;
&HÉÊ
PubChem′sBioAssaydatabase
±mB°Â#ö_ñ.¼
n©.pS(
,
!#S(©.p¼ns¾È
,
§O~l$°Âª©.p&Ê8oè
。
ymO~l
*Ñ.ËÌ$
17
ñ#ö_ñ.ç¾à{Ñ°
OGD/R
·v
H9c2
Sc¿jæ°}
;
B~pLMyàº
,15
ñ°Â
#ö_ñ.ªScOPYZnoÉÊfô;Ëà^_²q@N
、
®=<@N
、
äïöOP
、
¾¿jÏÐ
。
µ
yU¿O~lmBScOPÉÊ
,
!-.CÌOPÉÊ«@Ò¥
、
¥pq%ûàÉÊT
。
µ^y¯
¼O~lʤFS?Ñ6¿ÈÀ¹Ì
。
[
qrs
]
O~l
;
ScOP
;^
gÔZ
/
ð^Ø
;
°Â
;
nopq
[
tu)(
] 20150916
[
vwxT
]
@`ü¨g*xy
(81222051,81530097);
@`
“
a?HZ°ä
”
ü«a?éx
(2012ZX09301002002002,2012ZX09304
005)
[
yzA{
]
-
,
°
,
éÏj
,Tel:(010)82802719,Email:yongjiang@bjmueducn;
-±
,
Í°
,
ÎéÏj
,Tel:(010)
82805103,Email:lijun@bjmueducn
[
A{
]
Ø*Æ
,
Îqré
,Email:shuzeliu0915@163com
ActivecompoundsfromBaoyuandecoctionwithmyocardialprotection
activitiesandtheirpotentialtargets
SHUZeliu,ZENGKewu,MAXiaoli,TUPengfei,LIJun,JIANGYong
(StateKeyLaboratoryofNaturalandBiomimeticDrugs,SchoolofPharmaceuticalSciences,Peking
University,Beijing100191,China)
[Abstract] Baoyuandecoction(BYD)isaclassicalChineseformulaforcoronaryheartdiseasewithQideficiency,bloodstasistoni
fyingQiandYangdeficiencyHowever,thechemicalmaterialbasisandunderlyingactionmechanismsofBYDstillacksystemicstu
dyInordertoclarifytheactivecompoundsandthepotentialactionmechanismsofBYD,theoxygenglucosedeprivation/recovery
(OGD/R)inducedH9c2celsinjurymodelswasusedtoscreenthemonomericcompoundsofBYDwithmyocardialprotectionactivity
PubChem′sBioAssaydatabasewasthenusedtoanalyzethepotentialtargetsofactivemonomericcompounds,classifythepredictedbio
logicaltargets,andanalyzetheinternalrelationbetweenactivecompoundsofBYDandbiologicaltargetsThescreeningresultsshowed
thatBYDaqueousextractand17monomericcompoundscouldsignificantlyincreasethesurvivalrateofOGD/RinducedH9c2myocar
dialcelsTheresultsofvirtualtargetsscreeningstudyshowedthat15monomericcompoundsandthepotentialmechanismsformyo
cardialprotectionwererelatedtooxidativestresspathway,calciumionpathway,mitochondrialprotection,antiapoptosis,etc
TheseresultsverifiedthatBYDhadmyocardialprotectionefect,whichwasobtainedbynetworkregulationofmulticomponents
andmultitargetsAltheseresultsprovidethetheoreticalbasisandreferencesfortheclinicalusageofBYDintreatmentofcoro
naryheartdisease
·229·
OXÏ
:
O~l$mBScOPÉÊ°ÂËÌnoÉÊpq
[Keywords] Baoyuandecoction(BYD);myocardialprotection;oxygenglucosedeprivationrecoverymodel;activecompounds;po
tentialtargets
doi:10.4268/cjcmm20160527
SÅÆÇT?0¯Íi&Hw¡S©
,
ùSÅÆÇm?®ì$
,
F
S?çQX
。
FS?«F¹ÆÇm©¹Â(
Õ_?ùéÆÇñàrÃ
,
òScdÆ
、
d^r¯ùvQSÄ?
。
üPéFS?
m©0¯A,,åq«¬
。
O~l
(Baoyuandecoction,BYD)
«×%ÏÒ
-
,
!¤CP+Äsø{
《
g-SÒ
》[1],
Bð
ßf&W
,
¼;ʤFS?BÆr)f
B
[25]。
äùZ¤
BYD
,W.£»Ë
ÉÊfôkdï^
[67]。
4^ÉÊ^gÔZ
/
ð^
(OGD/R)
·vSc¿j¬KØöÖ~
FS??¢
,
±
BYD
Ñ-.ËÌ#ö_ñ.
¼n°ÂLM
,
!±°Â#ö_ñ.¼n
BioAssay
§
,
2±
BYD
FS?noÉÊfô¼n
¥(
。
1
q
11
O~lËÑ-¶
O~l,Û)
、
Ù¹
、
å
T
(
Z
)、
³Ä
(6∶2∶2∶1)4
,{
,
,íˤ
¶2Ä5%,4
,
Ï23w,}°ä,.
[ÔBcôÒ×
,
Û)¯1&\.ðÛ)
As
tragalusmembranaceus(Fisch)Bgevarmongolicus
(Bge)Hsiao
$ZÝÞ
,
Ù¹¯Aù&\.
Ù¹
PanaxginsengCAMey
$Z
,
å
T¯1&\.åT
GlycyrhizauralensisFish
$Z
Ï\ôHÝÞ
,
³Ä¯Ý&\.³Ä
CinnamomumcasiaPresl
$ZJ
。
©,4O
æo23w$A,P_$S
,
/<ׯ
AMAG20130312, PGAG20130312, GUAG
20130312,CCAG20130312。
O~lôõg`¯
:
Û)ÝÞ
30kg,
Ù¹ó%
10kg,
ZåTÝÞ
10kg,
³Ä«Þ
5kg,4
,Ã
6∶2∶2∶1
íñH
,
ù*
550L
ÏÒ¡
,
ï̵¥Ñ
-
2h。
=*Ñ+,*
,
,*ù
440L
*
,
ï
̵¥Ñ-
2h,
Ñ-
2
ö
。
ÇHñ!
3
ö¥+!w
̵
,
¢9$ZHáÎ
BYD
%¥
165kg。
,
Ñ-}¯
30%。
BYD
$#ö_ñ.[D4TU
8O~l$
=Ò×_ñ.
[67],
2Ë8º@@¡©.&(
BCDEËL
BYD4
,$±ÄÖ
133
ñ
,
ƱÏ
HPLC
Å(
,
w¤
98%。
12
Ë|
¿j
H9c2
Sc¿jËã$%A
&}£»Aø¿j$S
(
23
)。DMEM
°gج+
(
Ç%
Hyclone);
+Æw
(FBS)(
Ç
%
Hyclone);025%
]$
EDTA
F_+
(
Ç%
Gib
co);MTT(
Ç%
Sigma);
gaE
96
Õò ¬Ù
(
Ç%
BDFalcon)。
13
u
MCO15AC
<^_á¬Z
(
{4
SANYO);
>]J
(
23QÑý&!]_gÓD
E
);YXQLSSⅡõÌæ½FSu(¼HgïT
)BCDEAõj
);
$
(
³%
Tecan);BS
110S
U<°Ñ
(
³%
Sartorius);
J°=Sf
(
³%
Eppendorf)。
2
¶
21 H9c2
Sc¿j
OGD/R
ØÊõª,.úÈ
H9c2
wxSc¿j¬¤,B
10%
+Æw
、
úì
(100U·mL-1)、
\ì
(100U·mL-1)
DMEM
¬+$
,
! Co
95%
!
,5% CO237
℃
¬Z$©ý
。
TUý
,
#
H9c2
wxSc¿j
/¤¬Ù$¬
24h,
¿j.±¯
10×105
ñ
/
mL,
¬
24h
H
,
#¿j¬+ÀÂ!ù
gÆw¬+
,
¬¤
95% N2,5% CO237
℃
¬+$6d
4h,
òdgd^
(OGD)
¬K
。
OGD
&H
,
Y²¬+ÀÂ
,
ù,Bï
DMEM
¬+
,
o
95%
!
、5% CO237℃¬
Z$ͬ
24h
ð^ðgMu
,
n[ÒÓá
¯^gÔ=
/
ð^
(OGD/R)
¬KÒÓ
。
:浯
±]G±
BYD(50,100,200,400,600,800,
1000mg·L-1)
BYD
$
133
ñ#ö_ñ.
(
G±
400μmol·L-1)¼n°ÂLM。
22
:Ê
PubChemBioAssay
§
BYD
$ó°
Â#ö_ñ.
B
PubChem
;^
,
8
Chemical
structuresearch
¼§Å:S
,
q*z×
/
Y
Â
(identity/similarity)
ú
,
¼W^J¯
mol
_ñ.§
,
½Û
Options
8#
,
×Y±≥90%。
q*Å:HoySzÉÅ:_¼n
BioActiv
·329·
2016
y
3
z ©
41
ª©
5
}
Vol41,No.5 March,2016
ityAnalysis,
ÇM
Targets
ú
。Targets
ó«
PubChem
Ǭpy
,
MÌ-ý
10
ÉÊp
¼nÍó
,
)¿ÒÓx^
[8]。
3
y
31 BYD
Ñ°
OGD/R
·v
H9c2
¿j¬KØ
æ°}
ª±Ä{Y§
,OGD/R
Ø{¿jæ
°}Cà_þ
(P<0001),
-Ø{¿jæ°
}GHæ°é1
40% ~60%,
zCò
;
ª
OGD/R
Ø{Y§
,
]G±
BYD
{
(50,100,
200,400,600,800,1000mg·L-1)
íçCàÑ°Í
¬Sc¿jæ°}
,
-(
BYD
G±Ñ°
,
S
c¿jæ°}BÑ°±
,
xó
1。
ó
1
]G±
BYD
Ñ°
OGD/R
·v
H9c2
¿j¬K
Øæ°}
(珋x±s,n=4)
Table1 DiferentconcentrationsofBYDenhancedthecelvia
bilitiesinOGD/Rinjury(珋x±s,n=4)
{×
G±
/mg·L-1 ¿jæ°}/%
±Ä
- 9972±110
OGD/R - 5316±3551)
BYD 50 6001±3402)
100 6893±1023)
200 7360±1563)
400 8684±1303)
600 9600±5003)
800 10784±2303)
1000 11866±4373)
¶
:
ª±Ä{Y§
1)P<0001;
ªØ{
(OGD/R)
Y§
2)P<
001,3)P<0001。
32 BYD
$#ö_ñ.o
OGD/R
·v
H9c2
¿
j¬Kؼ°ÂLM
±8
BYD
rÌ
4
{
,$=
133
ñ#ö_ñ.
,
ÉÊ
OGD/R
·v
H9c2
¿j¬Kؼn¿LM
,
Ì$
17
ñ
_ñ.óÂà{,È°Â
,
×:>¤Û)
、
Ù
¹
、
³ÄåT
4
,
,
óC
BYD
$
4
,
$í[,°Â_ñ.
,
zCðFGñÈÂã
Â
。
°Â_ñ.±
OGD/R
·v
H9c2
¿j¬
KØ¿jæ°}%&yËÌ_ñ.:>x
ó
2。
33 BYD
$°Â©.p§
±
BYD
$
17
ñóÂmBOPSc¿j°Â#ö_ñ
.¼n
PubChemBioAssay
§
,
Ì$
9
<
、10
<_ñ
.¯TU
Qö=Ú_ñ.
,
àBYZ©.°
ó2 BYD$#ö_ñ.Ï OGD/R·v H9c2¿j¬K
Ø°ÂLMyË:>Íó
(珋x±s,n=3)
Table2 ThelistofactivecompoundsfromBYDoncelviabili
tiesforthecardiomyocytesexposedtoOGD/Rtreatmentand
theirsources(珋x±s,n=3)
{× _ñ.-³ ¿jæ°}
/%
:>
±Ä
100±021
OGD/R 6169±4041)
1 isomucronulatol7O
βDglucoside
7960±5224) Astragalusmembran
ceus
2 astragalin 7134±2843) Amembranceus
3 astragalosideⅡ 7238±4012) Amembranceus
4 benzoicacid 7589±1703) Cinnamomumcasia
5 4hydroxytranscin
namicacid
7691±2043) Ccasia
6 fareanol 7640±3363) Ccasia
7 isolariciresinol 7539±5063) Ccasia
8 5methoxyisolaricir
esinol
7501±2693) Ccasia
9 (4carboxyl)phenol
5O( 4 hydroxy
benzoyl )βDapio
furanosyl(l→2)βD
glucopyranoside
7485±3623) Ccasia
10 (+)isolariciresinol
4OβDapiofuranosyl
(1→2)βDglucopyr
anoside
8216±7794) Ccasia
11 protocatechuicaldehyde 13194±22764)Ccasia
12 licuraside 7406±3283) Glycyrhizauralensis
13 7,2′,4′trihydroxy
isoflavan
8633±0974) Guralensis
14 2,4, 4′,βtetra
hydroxydihydrochalcone
8111±0674) Guralensis
15 uralsaponinAdime
thyester
7491±6043) Guralensis
16 20(S)ginsenosideRg2 11869±45104)Panaxginseng
17 cyclo(LLeuLTyr) 7352±5263) Pginseng
¶
:
ª±Ä{Y§
1)P<0001;
ªØ{
(OGD/R)
Y§
2)P<
005,3)P<001,4)P<0001。
Â=kB
,
ÌS
15
ñ_ñ.M-=§yÌ
-ý
10
X!ªFS?°±YZÉÊpq¼nÍ
ó
,
)½xó
3。
4
À
FS?ɯßÙÜÝ©¬wT?
,
m?}*y¼°
,
-´þ`_±
,
éFS?0
2]á
。
Sc\¯ScdÆ«¶¬K
(myo
cardialischemiareperfusioninjury,MIRI)
«FS?
Çïx?
,
-
MIRI
«FS?Ò
Ó$±ScÖ©]:%&;ÒÓ
。MIRI
·429·
OXÏ
:
O~l$mBScOPÉÊ°ÂËÌnoÉÊpq
ó
3 BYD
$°Â#ö_ñ.noÉÊpÍó
Table3 ThepotentialtargetslistofactivecompoundsfromBYD
_ñ. nopq
isomucronulatol7OβDglucoside polyphenoloxidase2
chainB,thestructureofwildtypehumanhadh2(17βhydroxysteroiddehydrogenasetype10)boundto
Nad+at12A
chainA,thestructureofwildtypehumanhadh2(17βhydroxysteroiddehydrogenasetype10)boundto
Nad+at12A
FADlinkedsulfhydryloxidaseALR
placentagrowthfactor
vascularendothelialgrowthfactorA
astragalin DNApolymerasekappa
aldosereductase
FADlinkedsulfhydryloxidaseALR
prolyl4hydroxylase,betapolypeptide
chainA,crystalstructureofthehuman2oxoglutarateoxygenaseloc390245
DNApolymeraseiota
dualspecificitytyrosinephosphorylationregulatedkinase1A
DNApolymerasebeta
astragalosideⅡ tyrosinase
orexinreceptortype1
nuclearreceptorRORgammaisoform1
chainA,humanbcl2incomplexwithbimbh3peptide
DNAdamageinducibletranscript3protein
nuclearreceptorRORgamma
benzoicacid nuclearfactorerythroid2relatedfactor2isoform1
carbonicanhydrase2
peroxisomeproliferatoractivatedreceptorgamma
vitaminD3receptorisoformVDRA
4hydroxytranscinnamicacid carbonicanhydrase2
carbonicanhydrase1
carbonicanhydrase9
carbonicanhydrase14
carbonicanhydrase12
carbonicanhydrase7
aldosereductase
aldoketoreductasefamily1memberB10
aldehydedehydrogenase1family,memberA1
fareanol calmodulin
isolariciresinol plateletactivatingfactoracetylhydrolaseIBsubunitbetaisoformb
arachidonate12lipoxygenase,12Stype
carbonicanhydrase
5methoxyisolariciresinol plateletactivatingfactoracetylhydrolaseprecursor
plasminogenprecursor
troponinⅠ,cardiacmuscle
protocatechuicaldehyde chainA,crystalstructureofthehuman2oxoglutarateoxygenaseloc390245
4aminobutyrateaminotransferase,mitochondrial
FADlinkedsulfhydryloxidaseALR
succinatesemialdehydedehydrogenase,mitochondrial
licuraside FADlinkedsulfhydryloxidaseALR
prolyl4hydroxylase,betapolypeptide
DNApolymerasekappa
dualspecificitytyrosinephosphorylationregulatedkinase1A
·529·
2016
y
3
z ©
41
ª©
5
}
Vol41,No.5 March,2016
Âó
3
_ñ. nopq
sodium/glucosecotransporter1
aldosereductase
DNApolymeraseiota
7,2′,4′trihydroxyisoflavan salidase
estrogenreceptorbeta
estrogenreceptor
tyrosineproteinphosphatasenonreceptortype1
estrogenreceptor
potassiumvoltagegatedchannelsubfamilyKQTmember2
polyphenoloxidase2
Smad3
2,4,4′,βtetrahydroxydihydrochalcone cytochromeP4503A4isoform1
Aldosereductase
estrogennuclearreceptoralpha
cytochromeP4502C19precursor
tyrosineproteinphosphatasenonreceptortype1
plateletactivatingfactoracetylhydrolaseIBsubunitbetaisoformb
celulartumorantigenp53
ARprotein
microtubuleassociatedproteintau
uralsaponinAdimethyester corticotropinreleasinghormonereceptor2
microphthalmiaassociatedtranscriptionfactorisoform1
nuclearfactorNFkappaBp105subunitisoform1
20(S)ginsenosideRg2 sodiumchannelproteintype10subunitalpha
nuclearfactorNFkappaBp105subunitisoform1
glycogensynthasekinase3beta
vasopressinV1areceptor
Cyclo(LLeuLTyr) mutypeopioidreceptor
deltatypeopioidreceptor
glutamatereceptor1
glutamatereceptor2
glutamatereceptor4
glutamatereceptor3
kappatypeopioidreceptor
m©fôª¥/®ìYZ
,
üã,£>
、
®>
、
ç Pz*
、
¿jÏÐ
、
β
,
®úi±n
.Ml
,
ÉÊwúã,£
、
wü®>
、
$SÎ
²
、
stç Pz
、
lÆÇ8J®<
、
Kô¿jÏ
Ð
,
0ϯé
MIRI
FS?¥/_`
BÄ
。
$AÑàÉʾö
、^
:ð
Ùö©°
、
m?fôËT?_
,
!É
Êð¯;$,±T?¼n
,
-á¿HA
W
。
$AÆÈÀ
,
ÉÊð°Æ,
SÆÇT?-á¿ëw
[9],
ü{-©
¹¢
、
ÓfAl
、
ð¸¹Þ
、
O~lo
SÆÇT?íBà{W
。
O~l
(BYD)
ɯFS?ÏÒ-
¼E>ʤFS?BÆr)fB
,
Ú
Z¤
BYD
,W.£»ËÌÉÊfôRÌkd
ï^
。
ñ$A±FS?ÆrÈâ
,
4
^ÉÊ£»E>^Ê
H9c2
Sc¿
j
[1014]
¼n
OGD/R
¬KúÈ
,
~FS?Ù
ïx?ÈMu
,
8ù±
BYD
ËÌ$#ö_ñ.¼
nScOP°ÂLM
。
yàº
,BYD
ËÌ
17
ñ
#ö_ñ.o
OGD/R
·v
H9c2
Sc¬KØ
¼óÂà{ScOP°Â
,
U¿
BYD
BW
Â!¢º¿Ì$;,W.£»
。
:Ê
Pub
Chem′sBioAssay
±óÂSÆÇOP°Â
15
ñ
0j#ö_ñ.¼nÉÊp=§
,
m
BYD
$
4
$,í,B°Â#ö_ñ.
,
-n._
ñ.oSÆÇOPÉÊfôª¥®ì
、
¥_
`BZ
。
Ì$_ñ.
1,2,4,5,11,12,14
nop
qªKô°Â^wùYZ
;
_ñ.
6,12,13,16,17
nopqª¿j=<@BlBZ
,
ç¾Kô
®=<>
;
_ñ.
1,13
nopqª½¼¿j
·629·
OXÏ
:
O~l$mBScOPÉÊ°ÂËÌnoÉÊpq
w8J¿j©ýBZ
;
_ñ.
3,17
nopq
ªKô¿jÏÐBZ
;
_ñ.
3,4,12,15,16
no
pq¯¹ªl¿j¼À
,
Kô¿jÏÐ
;
_ñ.
5,7,8,17
nopq¯¹ªl8J®<
;
_ñ.
15,16
nopqª
NFκB@NlBZ,8ùé
[¹Â(Õ_m©
。
yÖ
,
_ñ.
11
mBäï
öOPÉÊ
,
ç¾stç Pz
。
¯¿U¼Á_ñ.ªnopqYÉÊz
Â
,
ÿ¼n¿^^ï
,
mµ
15
ñ_ñ
.ímBFS?ÉÊkB
[1522],
ËÉÊ
fôª¼Á_ñ.S(noÉÊpq£4Y
。
ü
11
<_ñ./¡¨©o
OGD/R
·v
H9c2
Sc¿j¬KØ$óÂëà{¿jOP°
Â
,
Ìnopq§yàº
,
/¡¨©ª^_²
qËäïöÉÊ_`îçYZ
。
^àº
,
/
¡¨©É¯¸¹FS?;,W
,
ÌÉ
Êfô;[D¾^_ÉÊ
[23]、
Kô®=<°°
、
wsäïö8
ATP
FÉÊ
[24],
8ù^Sc¿
jóÍdƬK
。
n.yB:¤â¥/¡¨©m
BSÆÇOPÉÊ
,
OÑzC
PubChem′sBio
Assaydatabase
±$,noÉÊpqm3
ÊÂzÂ
。
4@Ò,WLMpS(Yñ
¶
,
-ç.C¿$,ðO~lScdÆ«
¶¬K,W.£»ËÌYZÉÊpq
,¯
Ì
ʤFS?Ñ6¿ÈÀ
,
OѯÌ
Ø$,ð,W.£»ËÉÊfôÑ6¿
?Ò¹Ì
。
[
|}?~
]
[1]
+Äs
g-SÒ
¼ª
[M]
abww$/&[
C£
yÊÚ5*c.24
[2]
\.
,
D9w
,
äo
,
O~l7¾
[J]
O£%A
%,
,1999,10(5):379
[3]
!d
ñvwr
©
63
ª
[M]
¼H
:
¼H&()Âæ
Þ
,1959:1316
[4]
¨yè
,¨
e
,
çO+
,
O~lFS?
22
TUÈù
[J]
T9$A-.
,1995,11(6):20
[5]
tfõ
,
®°
,
Cg
,
O~l¯;ï©*
ÂgÆÈùËTU
[J]
$A-.
,1985,895
(12):15
[6]
FãO
,
wCu
,
,
,
O~l$Û9=
§Ò×
[J]
$T,
,2010,41(5):696
[7] MaXL,YuQ,GuoXY,etalNitricoxideinhibitoryflavonoids
fromtraditionalChinesemedicineformulaBaoyuandecoction
[J]Fitoterapia,2015,103:252
[8]
1Hu
,
{W
,
Ûþd
,
£¤
PubChem
=ß°äÖ.
¬p¶
[J]
$T,
,2012,43(11):2099
[9]
1Õ3
,
1Ñ
.
$A,éSÆÇT?¡>ܱ
[J].
23$A
,2007,26(7):396.
[10] IsomatoS,KawakamiA,ArakaldT,etalEfectsofantiarhyth
micdrugsonapoptoticpathwaysinH9c2cardiaccels[J]J
PharmacolSci,2006,101(4):318
[11]
®I
,
Ûh
,
F÷
,
)_i·vwxSc¿j
H9c2
ÏÐ
ÉÊfô
[J]
§¹wk
:
Aæ
,2007,33(2):269
[12]
¤u
,
w
,
·:j
,
H9c2
Sc¿jûüg¼<¦·
4
¼Xfô
[J]
$ISÆÇ?-.
,2001,29(8):
500
[13] LiuL,ZhangXJ,JiangS,etalMolecularcloningofhumanheat
shockprotein27andstudyofitsprotectiveefectsonoxidative
damageinratcardiomyocteH9c2[J]JNanjingMedUniv,
2005,19(4):187
[14] AboutablME,EIKadiAOConstitutiveexpressionandinduc
ibilityofCYP1A1intheH9c2ratcardiomyoblastcels[J]Toxi
colinVitro,2007,21(8):1686
[15]
hCC
,
°N7
,
dk
,
Û)_˱ScdÆ
«¶¬KOPÉʼ½
[J]
$A,v²
,2015,32
(3):120
[16]
?³w
,
µ^í
,
õxÑ
,
Û)°ÂÑ-±ípÒ
^_¬KéPÉÊ
[J]
$%$,-.
,1996,21(12):
746
[17]
?³w
,
µ^í
,
õxÑ
,
Û)BW±^ã,£wú
ÉÊ
ESR
[J]
©._ª©..ȼ½
,1996,23
(3):260
[18]
?³w
,
µ^í
,
õxÑ
,
Û)uÛ9±
DNA
¬KéP
ÉÊ
[J]
©._ª©..ȼ½
,1996,23(4):
346
[19] MartinDP,CohenSMNucleophilerecognitionasanalternative
inhibitionmodeforbenzoicacidbasedcarbonicanhydraseinhibi
tors[J]ChemCommun,2012,48(43):5259
[20] LüJM,YaoQZ,ChenCYGinsengcompounds:anupdateon
theirmolecularmechanismsandmedicalapplications[J]Cur
VascPharm,2009,7(3):293
[21] WangJR,ZhouH,YiXQ,etalTotalginsenosidesofRadix
Ginsengmodulatestricarboxylicacidcycleproteinexpressionto
enhancecardiacenergymetabolisminischemicrathearttissues
[J]Molecules,2012,17(11):12746
[22]
0µ
²¹<ÐÃĶË+, §Ë̱wxbÂ
Sc\¯%&fô
[D]
ýº
:
§¹w
,2009
[23]
!ÉÕ
,¨
··
,
®Ã
/¡¨©,ȼ½
[J]
$%
TU|-.
,2013,19(23):338
[24] GaoY,WangN,ZhangY,etalMechanismofprotectiveefects
ofDanshenagainstironoverloadinducedinjuryinmice[J]J
Ethnopharmcol,2013,145(1):254
[
-0
]
·729·