全 文 ：
药理实验与临床观察

Vasodilatory effect of water decoction of dried flower of
Carthamus t inctorius on rabbit aorta in vitro
LI Hong- fang1, WANG Long-de2, PANG Jin- jiang1


( 1
Department of Physiology, Lanzhou Medical Colleg e, Lanzhou 730000, China;
2. Affiliated Hospital, Gansu College of TCM , Lanzhou 730020, China)


Abstract: Object
To observe the vasodilatory effect of a w ater decoct ion of the dried flower of Carthamus
tinctorius L. ( DFCT ) on rabbit thoracic aorta and its mechanism. Methods
Strips of rabbit aort ic smooth
muscle w ere suspended in organ baths containing Kreb
s solution, and then isometric tension w as measured. Re-
sults
DFCT did not change the rest ing tension of rabbit aort ic strips. But similar to Ach ( 10- 5 mol/ L) , DFCT
( 20 mg/ mL) could cause an obvious relax at ion in 10
- 6
mol/ L NA-precontracted arterial strips. T he relaxant ef-
fect of DFCT w as signif icantly reduced by removal of endothelium and 10- 4 mol/ L L-NNA and 10- 5 mol/ L
methylene blue but not by prostaglandin synthase inhibitor and blockage of adrenergic
receptor. In addit ion,
DFCT ( 40 mg/ mL) inhibited NA and KCl cumulative concentrat ion-response curves of aort ic strips w ithout en-
dothelium , and changed the PD2 values for NA from ( 6. 06
0. 09) in control g roup to ( 5. 07
0. 08) and for
KCl from ( 1. 71
0. 33) in control group to ( 1. 35
0. 20) , respect ively. Conclusion
T hese results suggest
that the vasodilatory effect of DFCT in rabbit thoracic aorta may be related to the nit ric ox ide release from en-
dothelium , and also probably due to inhibit ion of Ca2+ influx through receptor-operated and voltage-dependent
calcium channels.
Key words: the dried flower of Carthamus t inctor ius L. ; isolated aort ic st rip; endothelium cells; calcium
influx
红花水煎剂对家兔离体主动脉血管的舒张作用
李红芳1,汪龙德2, 庞锦江1
( 1
兰州医学院 生理教研室,甘肃 兰州
730000; 2
甘肃中医学院附属医院, 甘肃 兰州
730020)
摘
要:目的
观察红花 Car thamus tinctor ius ( DFCT ) 水煎剂对血管肌条的舒张作用及机制。方法
将家兔离体
主动脉肌条放置于灌流肌槽中,记录其等长收缩。结果
DFCT 对血管肌条静息张力无明显影响, 但 20 mg / mL
DFCT 水煎剂与 10- 5 mol/ L 乙酰胆碱相似, 可使 10- 6 mo l/ L 去甲肾上腺素预收缩血管肌条产生明显的舒张作用。
去除内皮细胞、10- 4 mo l/ L L-NNA 或 10- 5 mol/ L 甲烯蓝可减弱 DFCT 的舒张血管作用, 但前列腺素合成抑制剂
和
肾上腺素能受体阻断无明显影响。另外, 40 mg/ mL DFCT 水煎剂可明显抑制去内皮血管肌条去甲肾上腺和
KCl 的量效收缩反应,使其 PD2值分别由对照组 6
06
0
09 和 1
71
0
33 变为 5
07
0
08 和 1
35
0
20。结
论DFCT 水煎剂可通过受体操纵 Ca2+ 通道和电压依赖性 Ca2+ 通道抑制外 Ca2+ 内流, 使血管肌条舒张, 其作用与
内皮释放的 NO 有关。
关键词:红花; 离体血管肌条; 内皮细胞; 钙内流
中图分类号: R286
59


文献标识码: A


文章编号: 0253 2670( 2003) 05 0430 04


The dried flower of Carthamus t inctor ius L.
( DFCT) is a traditional Chinese medicine. It s differ-
ent preparations exhibit a w ide diversity of biologic
act ivit ies including ant-i coagulat ion [ 1] , ant-i inflam-
mat ion [ 2] , antitumor act ivit ies[ 3] . Their ant-i is-
chemia
[ 4]
, ant iox idat ive and fat igue-resist ing proper-

430
中草药
Chinese T raditional and Herbal Drugs
第 34 卷第 5 期 2003年 5月

收稿日期: 2002-09- 08基金项目:甘肃省科委中青年科技基金资助项目( YW991-A23-011)作者简介:李红芳( 1966
) ,女,甘肃省镇原县人, 1992年毕业于兰州医学院生理学专业,获医学硕士学位, 2002 年毕业于兰州大学生命科学学院生物学专业,获理学博士学位。现为兰州医学院生理教研室副教授,主要从事平滑肌生理与药理研究。
t ies[ 5] , their enzymatic inhibitory[ 6] and uterus exc-i
tory[ 7] ef fects have also been reported. Decoctions of
DFCT have been studied in the cardiovascular sys-
tem . Here a w eak inhibitory effect on the heart of
anesthet ized animals and a decrease in blood pres-
sure[ 8] , an increase in coronary blood flow and the
vasodilatory ef fect on the precontracted aorta
[ 9]
have
been reported, but the vasoconst riction effect on pe-
ripheral blood vessels in the ear has also been
found [ 10] . T herefore, the ef fect of w ater decoctions
of DFCT on vascular smooth muscle and its mecha-
nism are not completely clear. In this study, we have
examined the mechanism of act ion involved in the
vascular smooth muscle effect of DFCT on rabbit tho-
racic aorta.
1
Materials and methods
1
1
Drugs. DFCT ( ext racted and identified by
M edicine Inspect ion Inst itute of Gansu Province,
China) w as smashed into pieces, decocted in w ater
and made it into 100% concentrat ion of decoct ion ( g/
mL) ; N


- L-nit ro-arg inine ( L-NNA, Sigma ) , in-
domethacin ( Indo) ( Taicang, Jiangsu Province, Ch-i
na) w as dissolved in Na2CO3 solution and the pH was
adjusted to 7. 4; propranolol ( Prop) ( The Second
Pharmaceut ical Factory of Beijing , China) ; nora-
drenaline ( NA, Datong Huida, China) ; methylene
blue ( MB, M erck) ; acety choline ( Ach, Sigma) .
1
2
Arterial tension studies. Rabbits and arterial
st rips were prepared according to our previous
study[ 11] . Isometric tension was recorded w ith BL-
410 Experimental System of Biological Function
( TME, China) through an IBM computer. After 90
minutes of equilibrat ion, different experiments were
carrid out: ( 1) in some experiments, DFCT w as
added in progressively increasing cumulat ive concen-
trat ions ( 10, 30 and 70 mg / mL) in order to observe
its effect on the rest ing tension of aort ic strips. ( 2)
T o analyze if DFCT could relax an ex ist ing contrac-
t ion, arteriae w ith or w ithout endothelium were con-
tracted by NA ( 10- 6 mol/ L ) . When the contractile
response had reached a stable plateau ( approximately
5
10 minutes) DFCT ( 20 mg/ mL) or Ach ( 10- 5
mol/ L ) w as added respectively. ( 3) To evaluate the
possible mechanism of relaxation induced by DFCT in
NA-contracted aort ic st rips, the strips w ith endothe-
lium were contracted by NA and the response to
DFCT or Ach w as determined repeatedly after prein-
cubat ion 15 minutes w ith one of the follow ing sub-
stances: 10- 4 mol/ L L-NNA, 10- 5 mol/ L MB,
10- 5 mol/ L Indo and 10- 5 mol/ L Prop. ( 4) In add-i
t ional experiments, af ter st rips were stabilized under
2 g rest ing tension for 90 minutes in Krebs
solut ion,
the concentrat ion-response curve to NA ( 10- 7. 5

10- 5 mol/ L ) or KCl ( 10
100 mmol/ L ) w as ob-
served in the absence and presence of DFCT ( 40 mg/
mL) in rabbit aort ic st rips without endothelium.
1
3
Data analysis. All the results w ere expressed as
x
s . Relax at ion w as expressed as percentag e relax-
at ion of cont raction induced by NA ( 10- 6 mol/ L ) . In
experiments of the concentrat ion-response curves, the
results were expressed as percentage of cont rol con-
tract ile response induced by 10
- 5
mol/ L NA and 100
mmol/ L KCl respectively. Statistical analysis was
performed in the paired and unpaired student
s t-
test . Comparison among multiple groups w as made by
analysis of variance ( ANOVA) .
2
Results
2
1
Effects of DFCT on rest ing tension and NA-
precontract ion in rabbit aort ic strips. DFCT ( 10, 30
and 70 mg/ mL) administrated in progressively in-
creasing cumulat ive concentrations did not affect arte-
rial rest ing tension. How ever, DFCT ( 20 mg/ mL)
( F ig. 1 A) and Ach ( 10
- 5
mol/ L) ( F ig. 1 B) caused
( 56
15
3
85) % and ( 62
70
2
27) % relax at ion
of NA-precontracted st rips ( P< 0
001, n= 12) re-
spectively.
* * * P < 0
001 v s NS;


P< 0
001 v s DFCT
Fig. 1
Effects of L-NNA, MB, and Denude on rela-
xation induced by DFCT (20 mg/ mL) ( A) and
Ach ( 10- 5 mol/ L) ( B) in NA ( 10- 6 mol/ L)
precontracted isolated rabbit aortic strips
2
2
Effects of L-NNA, MB, denuded endothelium
( Denude) , Indo and Prop on responses to DFCT or

431
中草药
Chinese T raditional and Herbal Drugs
第 34 卷第 5 期 2003年 5月
Ach in NA-precontracted st rips. Incubat ion w ith L-
NNA ( 10- 4 mol/ L ) or MB ( 10- 5 mol/ L ) signif-i
cant ly reduced relaxat ion induced by DFCT or Ach in
rabbit aort ic st rips ( P< 0
001, n= 10) . Endothel-i
um removal also markedly decreased the relaxation
( P< 0
01, n = 10, F ig. 1 A for DFCT and Fig. 1 B
for Ach) . However, incubat ion w ith Indo ( 10
- 5
mol/ L) or Prop ( 10- 5 mol/ L ) did not affect relax-
ation induced by the two preparat ions ( P> 0
05, n
= 10, Fig. 2) .
Fig. 2
Effects of Indo and Prop on relaxation induced
by DFCT ( 20 mg/ mL) in NA (10
- 6
mol/ L)
precontracted isolated rabbit aortic strips
2
3
Effects of DFCT on NA and KCl concentrat ion-
dependent contract ile responses. The NA ( Fig . 3 A)
and KCl ( Fig. 3 B) concentrat ion-dependent contrac-
t ion curves were shif ted to the right after incubation
w ith DFCT ( 40 mg/ mL ) in rabbit arterial strips.
M ax imal contract ions for NA and KCl w ere reduced
to ( 54
72
4
58) % and ( 72
88
4
28) % respec-
t ively ( P< 0
001, n= 7) . T he PD2 values in control
and after incubation with DFCT ( 40 mg/ mL) were
( 6
06
0
09) and ( 5
07
0
08) for NA, and were
(1
71
0
33) and ( 1
35
0
20) for KCl, respec-
t ively.
1-cont rol group; 2-DFCT 40 mg/ mL
* P< 0
05
* * P < 0
01
* * * P< 0
001 vs cont rol group
Fig. 3
Effects of DFCT (40 mg/mL) on NA ( A)
and KCl (B) concentration-dependent
contraction curves in isolated rabbit aorta
3
Discussion


DFCT contains varied effect ive const ituents,
such as carthamone, carthamin, neocarthamin, saf-
flower-yellow, 15
, 20
-dihydroxy-
4-pregnen-3-one
and so on[ 12] , and its different preparations exhibit
ex tensive pharmacological act ions which w ere mainly
related to cardiovascular system[ 8] . Some researchers
reported that the decoct ion and w ater ex tract of
DFCT and saf flower-yellow could directly af fect the
tension of vascular smooth muscle, but the mecha-
nism involved in its act ions w ere not elucidated.
Results show n that the water decoction of DFCT
could relax aort ic st rips precontracted w ith NA in the
same manner as Ach, but did not affect their resting
tension. It is now recognized that vasodilatory re-
sponse to Ach are mainly mediated by release of nit ric
oxide ( NO) f rom endothelium[ 13] and NO can stimu-
late soluble guanyly l cyc- lase in smooth muscle cells to
increase the second messenger guanosine 3
, 5
-cyclic
monophosphate ( cGMP) , w hich is thought to lead to
relaxat ion largely via voltage- independent mecha-
nism. In our experiments, denuded or incubated rab-
bit aort ic st rips w ith L-NNA, an inhibitor of NO
synthesis significant ly decreased the relax at ion caused
by DFCT. MB, an inhibitor of cGMP synthesis also
could reduce the relax at ion induced by the prepara-
t ion. Our results suggest that in vi tro relaxation of
rabbit aorta caused by acute administ rat ion DFCT be
dependent on endothelium and probably relate to
cGMP.
The endothelium might also release a number of
prostaglandins, either vasodilator or const rictor. In
our experiments, Indo did not affect relaxation in-
duced by DFCT in endothelium-intact aorta. Prop,
an antagonist of adrenergic
receptor, also did not af-
fect the vasorelax at ion. These results indicate that
the release of vasodilator prostanoids and adrenergic

receptor are not associated w ith aort ic relax at ion in-
duced by DFCT .
Noradrenaline ( NA) can act ivate receptor-oper-
ated calcium channels ( ROCs) in cellular membrane
of vascular smooth muscle and increase calcium in-
flux , meanwhile can also act ivate G proteins and
phospholipase C to produce inositol t risphosphate
( IP3) w hich causes calcium release f rom endoplasmic
ret iculum
[ 14]
. Potential dependent calcium channels
( PDCs) are act ivated by depolarizat ion of the plasma

432
中草药
Chinese T raditional and Herbal Drugs
第 34 卷第 5 期 2003年 5月
membrane when the ext racellular K+ concentraction
is increased[ 14] . In the present study, DFCT shifted
the NA and KCl concentrat ion-response curves to the
right. These results might ref lect the inhibit ion of
calcium influx into the cellular cytoplasm which are
supported by those prev iously reports that DFCT
could markedly block calcium inf lux through ROCs
and PDCs in cellular membrane of vascular smooth
muscle according to 45 Ca across-membrane measure-
ment [ 15] . In this w ay, the vasodilator effect of DFCT
has been associated with an inhibitory modulat ion of
calcium entry into vascular smooth muscle.
In conclusion, our results indicate that , in rabbit
thoracic aorta, the w ater decoction of DFCT exhibits
a vasodilatory ef fect on contract ion induced by NA,
w hich is related to endothelium and involved in NO.
Also, this vascular relaxation probably is mediated by
inhibit ion of calcium influx via ROCs and PDCs.
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人参茎叶皂苷对失血性休克大鼠糖皮质激素受体的影响
凌昌全1,李
敏2,苏永华1,李
勇1,黄雪强1, 沈志雷2,谭金兴3

( 1
第二军医大学长海医院 中医科, 上海
200433; 2
第二军医大学 军队卫生学教研室, 上海
200433; 3
第二军医大学
病理生理学教研室,上海
200433)
摘
要:目的
观察人参茎叶皂苷 ( ginsenosides, GSS) 对失血性休克大鼠糖皮质激素受体 ( GR) 的影响, 并分析其
作用机制,为研制及时抢救失血性休克患者的天然药物制剂提供实验依据。方法
雄性 SD 大鼠随机分为失血性
休克组和对照组,失血性休克组分别每日 ig 200, 100, 50 mg / kg GSS 水溶液, 对照组和模型组 ig 蒸馏水 2 mL, 共
10 d。以 [ 3H] 地塞米松为配体,用一点分析法测脑和肝胞液 GR 结合活性 ( Rs)、半定量 RT-PCR 方法测肝胞液
GR mRNA 水平、放免法测血浆促肾上腺皮质激素 ( ACTH) 和皮质酮 ( GC) 浓度。结果
GSS 组大鼠脑和肝胞液
的 GR 结合活性高于单纯失血性休克组, 其中以中剂量组最明显 ( P < 0
01) ; GSS 组大鼠肝胞液 GR mRNA 表达
水平高于单纯失血性休克组; GSS 组大鼠血浆 ACTH 和 GC 浓度和单纯失血性休克组没有明显差别。结论
GSS

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中草药
Chinese T raditional and Herbal Drugs
第 34 卷第 5 期 2003年 5月

收稿日期: 2002-08- 24基金项目:国家杰出青年基金资助项目 ( 30025045) ; 国家自然科学基金面上项目 ( 30271675)
作者简介:凌昌全( 1957
) ,男,安徽怀宁人,医学博士,博士研究生导师,主任医师,教授,专业研究方向为中西医结合。