全 文 ：A PS 存在的条件下诱生的DC s 刺激自体和异体 T
淋巴细胞的能力显著高于无A PS 存在条件下诱生
的DC s, 再次表明前者诱生的DC s 具有更为成熟的
免疫表型。
A PS 是当归中的重要成分, 已有实验表明A PS
能从 mRNA 水平与蛋白质水平调控 GM 2CSF 的
表达, A PS 可能通过直接或间接途径促进淋巴细
胞、造血微环境中的基质细胞、巨噬细胞合成和分泌
GM 2CSF 或其他造血生长因子。研究表明,A PS 能
在体外促进小鼠脾淋巴细胞 IFN 2Χ的分泌和提高
IFN 2Χ的生物活性[15 ]。而 IFN 2Χ能促进DC s 的成
熟[16 ]。在本实验中, 推测 A PS 对 DC s 的刺激作用
机制可能为: (1) 增强骨髓细胞 GM 2CSF 自分泌作
用。 (2)诱导骨髓细胞 IFN 2Χ分泌增加。
目前, DC s 用于肿瘤免疫治疗存在两个方面难
题, 一方面, 尚未找到能大量扩增DC s 的因子。另一
方面, 扩增到一定时间和一定数量规模的DC s 是否
仍能保留其良好的抗原呈递功能。本研究结果表明
A PS 能提高DC s 的表面共刺激分子的表达, 促进其
成熟并提高存活率, 延长DC s 的生存时间。这预示
A PS 与其他细胞因子联合诱导CM L 2DC s, 对慢性粒
细胞白血病的治疗可能有良好的前景。
References:
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cells from hum an ch ron ic m yelomonocytic leukem ic cells in
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[ 2 ]　Yuan L Y, Chen G A , X iao X B, et a l. Study on the induc2
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液学杂志) , 2001, 14 (Supp l) : 272291
[ 3 ]　W esterm ann J , Kopp J1 Bcröab l au to logous dendrit ic cells
fo r vaccination in ch ron ic m yelo id leukem ia [J ]1 B one M ar2
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[ 4 ]　O rsin i E, Foa R 1 D endrit ic cell generation fo r leukem ia im 2
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[ 5 ]　Zheng M , W ang Y P1 Experim en tal study on effect of A n2
g elica po lysaccharide in inh ib ito ry p ro liferation and inducing
differen tiation of K562 cells [J ]1 Ch in J In teg ra ted T rad it
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[ 6 ]　Knigh t S C, H unt R , Do re C, et a l. Influence of dendrit ic
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[ 7 ]　M ayo rdomo J I, Zo rina T L , StrokusW J , et a l. Bone m ar2
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t ides elicit p ro tective and therapeu tic an titumour imm unity
[J ]1 N at M ed , 1995, 1 (12) : 1297213021
[ 8 ]　Grabbe S, Beissert S, Schw arz T , et a l. D endrit ic cells as
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[ 9 ]　Choudhury A , Gajew sk i J L , L iang J C, et a l. U se of
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[ 10 ]　E ib l B, Ebner S, D uba C, et a l. D endrit ic cells generated
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[ 13 ]　Feng J Q , L iu Z X, Zuo Z Y, et a l. T he effect of D anggu i
po lysaccharides and D anggu i lactone on cellu lar imm unity in
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[ 14 ]　Chen X, Regn S, Raffegerst S, et a l. In terferon alpha in
com bination w ith GM 2CSF induces the differen tiation of
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[ 15 ]　Shan J J , W ang Y, W ang S C, et a l. Effect of A ng elica sine2
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Cen tra l Imm unol, 2002, 3 (1) : 14.
Effect of polydatin on endothel ia l function in aorta vascular str ips
of hea lthy rabbits treated with ADM A
Q IN J ian1, CH EN Yun2zhen1, ZHOU Q i2x in2, SH I R uo2fei3, J IAN G Q ing2song2, LOU Q in4Ξ
(1. D epartm ent of Cardio logy, Co llege of C lin icalM edicine; 2. D epartm ent of Pharm aco logy, Co llege of Basic M edicine;
Chongqing M edical U niversity, Chongqing 400016, Ch ina; 3. Chongqing Em ergency Care Center, Chongqing 400020,
Ch ina; 4. L ib rary, Co llege of C lin icalM edicine, Chongqing M edical U niversity, Chongqing 400016, Ch ina)
　　Abstract: Object　To study the effect of po lydat in (PD ) and asymm etric d im ethylarg in ine (ADM A )
·535·中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 5 期 2004 年 5 月
Ξ 收稿日期: 2003209219
作者简介: 秦　俭 (1966—) , 女, 四川隆昌人, 副教授, 博士, 主要从事动脉粥样硬化的防治工作。E2m ail: HJQ J2001@Yahoo. com. cn
on the endo thelia l funct ion in ao rta vascu lar st rip s of healthy rabb its and the in teract ion betw een PD and
ADM A. M ethods　Do se2respon se cu rves of phenyleph rine (PE ) on the ao rt ic st rip s w ith o r w ithou t
ADM A andöo r PD. Em ax and K d from PE w ere ob ta ined and compared. Results　N o rm al ao rt ic st rip s
cou ld no t respond to ADM A. P retrea tm en t w ith either PD o r ADM A had no effect on the con tract ive
respon se of ao rt ic st rip s to PE. Bu t PD cou ld sign if ican t ly w eaken the con tract ive respon se of ao rt ic st rip s
p retrea ted w ith ADM A cau sed by PE in a do se2dependen t m anner, increase K d and decrease Em ax of PE.
Conclusion　E ither ADM A o r PD alone does no t influence the no rm al ao rt ic st rip con tract ive funct ion s,
the PE affin ity to Α2recep to r, and Em ax. Bu t PD cou ld noncompet it ively an tagon ize the con tract ive react ion
of ao rt ic st rip s to PE in the p resence of ADM A.
Key words: po lydat in (PD ) ; asymm etric d im ethylarg in ine (ADM A ) ; n it ric ox ide syn thase; phenyl2
eph rine (PE)
虎杖苷对 ADM A 作用的正常兔主动脉血管条内皮功能的影响
秦　俭1, 陈运贞1, 周岐新2, 史若飞3, 蒋青松2, 娄　钦4
(11 重庆医科大学临床学院 心内科, 重庆　400016; 21 重庆医科大学基础医学院 药理教研室, 重庆　400014;
31 重庆市急救中心, 重庆　400020; 41 重庆医科大学临床学院 图书馆, 重庆　400016)
摘　要: 目的　研究虎杖苷 (PD ) 与非对称性二甲基精氨酸 (ADM A ) 对正常兔主动脉血管条内皮功能的影响及
PD 与ADM A 之间的相互作用。方法　通过绘制主动脉条在 ADM A 与 PD 分别作用和共同作用时对苯肾上腺素
(PE) 的收缩量2效曲线, 计算并比较 Em ax和 K d 值。结果　正常主动脉条对ADM A 无反应, PD 或ADM A 预处理
后亦不影响其对 PE 的收缩反应。但 PD 使受ADM A 预处理的主动脉条对 PE 的收缩反应呈剂量依赖性减弱, 并
引起 K d 值增大、Em ax减小。结论　ADM A 或 PD 单独作用并不影响正常主动脉条的收缩功能及 PE 对 Α2受体的亲
和力和 Em ax; 但在 ADM A 存在时, PD 能非竞争性拮抗主动脉条对 PE 的收缩反应。
关键词: 虎杖苷; 非对称性二甲基精氨酸; 一氧化氮合酶; 苯肾上腺素
中图分类号: R 28612　　　文献标识码: A 　　　文章编号: 0253 2670 (2004) 05 0535 04
　 　 Endogenou s NO S inh ib ito r—asymm etric
d im ethylarg in ine (ADM A ) is a k ind of m ethyla ted
arg in ines. R ecen t studies show that its p lasm a
level is sign if ican t ly elevated in condit ion s includ2
ing athero sclero sis and its rela ted risk facto rs,
such as hyperten sion, d iabetes and hypercho les2
tero lem ia. T here have been som e repo rts on the
change of vascu lar endo thelia l funct ion cau sed by
ADM A [1 ] and in teract ion of ADM A w ith vasoac2
t ive sub stances[2 ] in vascu lar con tract ive and dila2
t ive funct ion s. Po lydat in ( 3, 4′, 52t rihydro2
st ilbene232Β2D 2glyco side, PD ) w as repo rted no t
on ly to have the effect of p romo ting calcium ion to
en ter vascu lar smoo th m u scle cell[3 ] , bu t a lso to
decrease the p ressu re of pu lmonary artery [4 ].
T here has been no repo rt on the in teract ion be2
tw een PD and ADM A on vascu lar con tract ive and
dila t ive funct ion s. T h is is the m ain aim of the p re2
sen t study.
1　M a ter ia ls and m ethods
1. 1　D rugs: Phenyleph rine (PE, H efeng Pharm a2
cy, Shanghai) , ADM A (Sigm a) , PD (Supp lied by
P rof. X IA Zh i2ling, from Chongqing U n iversity).
P oly g onum cusp id a tum Sieb. et Zucc. w as pu r2
chased from Chongqing Tongjunge Pharm acy. Its
m ain componen ts w ere po lydat in (PD ) , emodin,
an th raglyco side A , and ch rysophano l. T he PD
con ten t [ (59. 11±6. 65) % , n = 15 ] w as kep t as
the quality index of P. cusp id a tum . PD is a k ind of
ligh t yellow pow der. It is easy to be damp and is
d isso lved in ion2free w ater befo re the experim en t.
1. 2 　 T issue p repara t ion: F ive healthy m ale
Japanese rabb its w eigh ing 3. 00—3. 25 kg (pu r2
chased from Experim en ta l A n im al Cen tre of
Chongqing U n iversity of M edical Sciences) w ere
k illed by air em bo lism. T he tho racic ao rta w as cu t
ou t imm edia tely and the connect ive t issue around it
w as removed. T hen the ao rta w as p laced in to
K reb s’ so lu t ion w h ich w as kep t a t 37 ℃ and cu t in2
to sp ira l st rip. T he strip s w ere p reloaded w ith 2 g
·635· 中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 5 期 2004 年 5 月
w eigh t and equ ilib ra ted fo r a t least 1 h. D u ring the
w ho le experim en t, the incubat ion system w as aer2
ated w ith a gas m ix tu re of 95% O 2 and 5% CO 2.
T he change of ao rt ic st rip ten sion w as reco rded by
LM S—2B physio logy reco rder.
1. 3　R espon ses of ao rt ic st rip s to differen t drugs
1. 3. 1 　Cum u lat ive do se2respon se cu rve of PE:
A fter the equ ilib ra t ion period, d ifferen t concen tra2
t ion s of PE w ere added in to the bath tub. T he final
concen tra t ion s of PE w ere from 1×10- 9 to 1×10- 4
mo löL. T he change of the ten sion in the st rip w as
reco rded sim u ltaneou sly. Em ax and EC 50 w ere calcu2
la ted acco rd ing to Scatchard m ethod.
1. 3. 2　 Influence of ADM A on Em ax and K d in2
duced by PE: In o rder to ob serve w hether ADM A
cou ld induce the con tract ion of ao rt ic st rip , f ina l
concen tra t ion s of 1×10- 6, 1×10- 5, and 1×10- 4
mo löL ADM A w ere added in to the bath tub sepa2
ra tely. T hen the do se2respon se cu rve of PE w as
p repared, Em ax and K d w ere calcu la ted acco rd ing to
the fo rm er m ethod.
1. 3. 3　 Influence of PD on Em ax and K d induced by
PE: D ifferen t concen tra t ion s of PD (0, 1×10- 6,
1×10- 5, and 1×10- 4 mo löL ) w ere added in to the
bath tub, the influence of PD on the do se2respon se
cu rve of PE w as ob served. Em ax and K d w ere calcu2
la ted, too.
1. 3. 4　Effect of PD 2p retrea tm en t on funct ion of
ao rt ic vascu lar st rip in the p resence of ADM A :
A o rt ic st rip w as trea ted w ith variou s concen tra2
t ion s of PD (1×10- 6, 1×10- 5, and 1×10- 4 mo lö
L ) , 1 × 10- 5 mo löL ADM A , then the do se2re2
spon se cu rve of PE w as p repared, Em ax and K d
w ere calcu la ted.
1. 4　Stat ist ica l analysis: D ata w ere exp ressed as
x ±s. Sta t ist ica l analysis w as done w ith SA S soft2
w are package.
2　Results
2. 1　Em ax and K d values of PE: Em ax and K d values
w ere show n in T ab le 1.
2. 2　 Influence of ADM A on Em ax and K d induced
by PE: D ifferen t concen tra t ion s of ADM A ( 1×
10- 6, 1×10- 5, and 1×10- 4 mo löL ) cou ldn’t in2
duce no rm al ao rt ic st rip ’s con tract ion. Influence of
ADM A on Em ax and K d induced by PE w as show n
in T ab le 1. It show ed that ADM A didn’t affect the
ao rt ic st rip ’s con tra t ive respon se to PE.
2. 3　 Influence of PD on Em ax and K d induced by
PE: N either cou ld PD evoke any respon ses of
healthy ao rt ic st rip s, no r affect Em ax and K d values
induced by PE. Em ax and K d values w ere show n in
T ab le 2.
2. 4　Effect of PD 2p retrea tm en t on funct ion of ao r2
t ic vascu lar st rip in p resence of ADM A : PD cou ld
sign if ican t ly w eaken the con tract ion of ao rt ic st rip s
p retrea ted w ith AM DA induced by PE in a do se2
dependan t m anner. PD , 1 × 10- 4 mo löL cou ld
increase K d value sign if ican t ly. It w as suggested
that PD can noncompet it ively an tagon ize theΑ2recep to r’s con tract ive react ion to PE w hen PD
and ADM A coex isted at the sam e t im e. Em ax and
K d values w ere show n in T ab le 1.
Table 1　Emax and Kd values of con tractive respon se
of aortic str ips treated with ADM A andö
or PD induced by PE (x±s, n= 5)
Group s　　　 Em ax　　 K dö(1×10- 7 mo l·L - 1)　
PE (A ) 47167±20105 7104± 6115
10- 6 mo löL ADMA + PE (B) 58180±19103 5162± 5187
10- 5 mo löL ADMA + PE (C) 49198±16112 11180±10199
10- 4 mo löL ADMA + PE (D) 44160±14183※ 18131±17121
10- 6 mo löL PD+ 10- 5 mo löL ADMA + PE (E) 16189± 81793 ※★☆ 21101±11104
10- 5 mo löL PD+ 10- 5 mo löL ADMA + PE (F) 10108± 51973 ※★☆ 29153±41141
10- 4 mo löL PD+ 10- 5 mo löL ADMA + PE (G) 3107± 31593 ※★☆ 33136±261243 ※
　　3 P < 0101 vs group A ; 　※P < 0101 vs group B; 　★P < 0101 vs
group C; 　☆P < 0101 vs group D
Table 2　Emax and Kd values of con tractive respon se
of aortic str ips treated with PD induced
by PE (x±s, n= 5)
Group s PD ö(mo l·L - 1) Em ax K dö(1×10- 7 mo l·L - 1)
PE 61129± 5155 6124±4168
PD + PE 1×10- 6 78112±10109 5167±3145
1×10- 5 73136±11169 7182±5167
1×10- 4 62134±10186 7138±5101
3　D iscussion
　　T he p resen t experim en t w as designed to con2
f irm w hether ADM A had effect on con tract ive
funct ion of ao rt ic st rip s. T he resu lts show ed that
no rm al ao rt ic st rip s d id no t respond to ADM A.
W hen the strip s w ere trea ted w ith ADM A , bo th
Em ax and K d values induced by PE didn’t change
obviou sly. PE is an Α2recep to r agon ist. T he above
·735·中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 5 期 2004 年 5 月
study show ed that neither d id ADM A cau se rest ing
ten sion of ao rt ic st rip , no r influence PE con tract ive
eff iciency and aff in ity to Α2recep to r on no rm al ao r2
t ic st rip. ADM A is an endogenou s NO S inh ib ito r;
som e repo rts suggested that it can con tract b lood
vessels, increase b lood p ressu re [2 ] , and decrease
the release of NO from endo thelia l cells[1 ]. Bu t the
study did no t suppo rt th is. It has been repo rted
that NO is a st ress modu la to r fo r the ten sion of
smoo th m u scle. Bu t it is unclear w hether NO cou ld
modu la te b lood vessel basa l ten sion. T he p resen t
study indica ted that NO did no t p rofoundly modu2
la te b lood vessel’s basal ten sion.
　　PD is the m ain ingredien t in P. cusp id a tum .
T here have been m any research repo rts abou t PD.
Bu t there are som e paradox among them in its
effect on smoo th m u scle and its modu la t ion effect
on calcium ion. J IN et a l. repo rted that PD ( in a
concen tra t ion of 4×10- 4 mo löL ) cou ld m ake no r2
m al smoo th m u scle cell m em b rane to be depo lar2
ized. T h is w as rela ted to bo th the open ing of ion
channel and the modu la t ion of Α2recep to r, h is2
tam ine recep to r, and calcium channel[3 ]; PD no t
on ly p romo ted calcium ion to en ter vascu lar
smoo th m u scle cell, bu t a lso induced the release of
in tracellu lar ca lcium. PD m igh t increase the con2
t ract ility of no rm al vascu lar smoo th m u scle and the
ten sion of no rm al vessel[5 ]. PD cou ld also adju st
vessel’s ten sion by p romo ting ex tracellu lar sodium
ion to flow in side [6 ]; PD can increase in tracellu lar
ca lcium concen tra t ion th rough the influx of ex tra2
cellu lar ca lcium [7, 8 ]. L I et a l. repo rted that PD
cou ld decrease the p ressu re of pu lmonary artery [4 ].
T he resu lts show ed that PD cou ld no t evoke any
respon se of rabb it ao rt ic vessels w hen PD w as u sed
to vessels a lone. W hen vessels w ere p re2t rea ted
w ith PD , PD cou ld no t change bo th Em ax and K d
values of PE con tracted by ao rt ic st rip s sign if i2
can t ly. T hese resu lts suggested that PD did no t
exert a sign if ican t influence on the no rm al modu la2
t ion and Α2recep to r2m ediated modu la t ion of smoo th
m u scle’s ten sion.
　　T he study show ed that PD cou ld an tagon ize
PE’s con tract ive effects w hen it w as u sed w ith AD 2
M A sim u ltaneou sly. It w as m an ifest becau se Em ax
w as decreased sign if ican t ly and K d values w ere in2
creased sign if ican t ly in a concen tra t ion2dependan t
m anner. T he p resen t resu lts show ed that the inh i2
b it ion of NO S cau sed by ADM A and the fo llow ing
decrease of NO w ere no t enough to induce vessel
con tract ion. PD cou ld no t on ly adju st the diso r2
dered NO S system in athero sclero sis, bu t a lso in2
crease eNO S’s act ivity (ou r unpub lished data ).
W hen the vessel w as expo sed to ADM A and PD
sim u ltaneou sly, PD m ay resto re the p roduct ion of
NO by endo thelium , therefo re st rengthen vessel’s
d ila t ive funct ion. A s a resu lt, it an tagon ized the
effect of PE on Α2recep to r. It cou ld be deduced that
PD cou ld adju st the diso rdered NO S system. T he
impo rtance w as that PD did no t sign if ican t ly affect
vessel’s con tract ive and dila t ive funct ion under
no rm al circum stances; how ever, in condit ion s,
such as athero sclero sis, then the concen tra t ion of
p lasm a ADM A increased sign if ican t ly, PD cou ld
exert its p ro tect ing effect on b lood vessels from
ADM A , an tagon ize PE’s act iva t ing effect to Α2re2
cep to r noncompet it ively, d ila te vessels, and im 2
p rove o rgan’s b lood supp ly.
References:
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nous inh ib ito r of n itric ox ide syn thase regu lates endo thelial
adhesiveness fo r monocytes [J ]1 J A m Coll Card iol, 2000,
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[ 2 ]　V allance P, L eone A , Calver A , et a l. A ccum ulation of an
endogenous inh ib ito r of n itric ox ide syn thesis in ch ron ic renal
failu re [J ]1 L ancet, 1992, 339 (8793) : 57225751
[ 3 ]　J in C H , Zhao K S. Influence of po lydatin on the m em 2
brane’s po ten tial of rat b lood vessel smoo th cell [J ]1 A cad J
F irst M ed Coll PL A (第一军医大学学报) , 1998, 18 ( 3) :
20222041
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·835· 中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 5 期 2004 年 5 月