全 文 ：Effect of 20S -protopanaxad iol sapon in s on blood l ip id m etabol ism
and an tiox idative activ ity in hyperl ip idem ia rats
SU ID a2yun, YU X iao2feng, QU Shao2chun, XU H ua2liα
(D epartm ent of Pharm aco logy, Schoo l of Pharm aceu tical Science, J ilin U niversity, Changchun 130021, Ch ina)
　　Abstract: Object　To ob serve the effect of 20S 2p ro topanaxadio l sapon in s from P anax qu inquef olium
(PPD S) on to ta l cho lestero l, lipop ro tein cho lestero l m etabo lism and an t iox idat ive act ivity in experim en ta l
hyperlip idem ia ra ts1M ethods　T he to ta l cho lestero l (TC) , lipop ro tein cho lestero l, and lip id perox idat ion
(L PO ) con ten ts, p ro stag landin I2 (PG I2) , th rom boxane A 2 (TXA 2) levels, superox ide dism u tase (SOD )
act ivity and b lood visco sity w ere m easu red in hyperlip idem ia ra ts w h ich have been given PPD S 25, 50, 100
m gö(kg·d) by ip , con t inuou sly fo r 12 days. In addit ion, fa t accum u lat ion in liver w as ob served. Results
T rig lyceride (T G) , TC, low den sity lipop ro tein cho lestero l (LDL 2c) in serum , TXA 2 in p lasm a, L PO in
serum and liver, and b lood visco sity w ere decreased sign if ican t ly; and h igh den sity lipop ro tein cho lestero l
(HDL 2c) in serum , PG I2 in p lasm a, and SOD in serum and liver w ere sign if ican t ly increased by given
PPD S [ 50, 100 m gö(kg·d) ] in experim en ta l hyperlip idem ia ra ts. M o reover, PPD S can decrease TCö
HDL 2c and LDL 2cöHDL 2c ra t io , increase PG I2öTXA 2 ra t io , and inh ib it fa t accum u lat ion in liver.
Conclusion 　 PPD S cou ld inh ib it arterio sclero sis by imp roving cho lestero l and lipop ro tein2cho lestero l
m etabo lism , supp ressing L PO , and increasing the act ivity of SOD 1
Key words: 20S 2p ro topanaxadio l sapon in s (PPD S ) ; hyperlip idem ia; b lood lip id m etabo lism ; free
radica l; PG I2öTXA 2; b lood visco sity
20S -原人参二醇皂苷对高脂血症大鼠血脂代谢的影响及其抗氧化作用
睢大　, 于晓风, 曲绍春, 徐华丽
(吉林大学药学院 药理教研室, 吉林 长春　130021)
摘　要: 目的　观察 20S 2原人参二醇皂苷 (PPD S)对实验性高脂血症大鼠血清总胆固醇 (TC)、脂蛋白2胆固醇代谢
的影响及其抗氧化作用。方法　PPD S 按 25, 50, 100 m gö(kg·d) 给大鼠连续 ip 12 d, 测血清 TC、脂蛋白2胆固醇
及脂质过氧化物 (L PO ) 含量, 血浆前列腺素 I2 (PG I2) , 血栓素A 2 (TXA 2) 水平, 血清和肝脏超氧化物歧化酶
(SOD ) 活性及全血黏度, 并观察肝脏脂肪沉积情况。结果　PPD S 50, 100 m gökg 能明显降低甘油三酯 (T G) , TC,
低密度脂蛋白胆固醇 (LDL 2c) , TXA 2,L PO 含量及全血黏度, 并能明显提高实验性高脂血症大鼠高密度脂蛋白胆
固醇 (HDL 2c) , PG I2含量及 SOD 活性, 亦能使 TCöHDL 2c 及 LDL 2cöHDL 2c 比值明显降低, PG I2öTXA 2比值明显
升高。病理检查可见肝脏脂肪沉积明显减轻。结论　PPD S 可能通过调节体内血脂代谢、提高 PG I2öTXA 2比值及纠
正自由基代谢紊乱发挥抗动脉硬化作用。
关键词: 20S 2原人参二醇皂苷; 高脂血症; 血脂代谢; 自由基; PG I2öTXA 2; 全血黏度
中图分类号: R 286126　　　文献标识码: A 　　　文章编号: 0253 2670 (2004) 04 0416 04
　　 F ree2rad ica l2induced lip id and b iom em b rane
perox idat ion of low den sity lipop ro tein (LDL ) and
eryth rocytes crit ica lly con tribu tes to the risk of hu2
m an athero sclero sis[1, 2 ]. T herefo re, inh ib it ion of
LDL and eryth rocytes perox idat ion by supp lem en2 ta t ion of variou s natu ra l andöo r syn thesized an t i2ox idan ts leads to a novel therapy m ethod [3 ]. V ita2m in C, a w ater so lub le an t iox idan t w h ich canreduce Α2tocopheroxyl rad ica l to regenera te Α2to2cophe2ro l, m ay be lim ited in the in terio r of LDL
·614· 中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 4 期 2004 年 4 月
α 收稿日期: 2003208212
基金项目: 吉林省科委科研基金资助项目 (96290121)
作者简介: 睢大　 (1957—) , 男, 吉林省长春市人, 博士, 教授, 博士生导师, 1995 年毕业于白求恩医科大学药理专业, 获医学硕士学位,
2002 年毕业于吉林大学基础医学院生理专业, 获理学博士学位, 主要从事心血管药理科研及新药研究。
T el: (0431) 5619660　E2m ail: dayuansu i@ 163. com
and b iom em b rane becau se of the lipophob icity of
the mo lecu le [4, 5 ].
　　 20S 2P ro topanaxadio l sapon in s ( PPD S ) w as
separa ted from to ta l sapon in s iso la ted from leaves
of P anax qu inquef olium L. O u r p reviou s study dis2
covered that PPD S has a cu re effect on acu te m y2
ocard ia l infarct ion. T he m echan ism of the effect is
no t on ly the rela t ion to b lock ing effect of ca lcium
channel bu t a lso to the inh ib it ion of sympathet ic
t ran sm it ter release and ren in angio ten sin sys2
tem [6, 7 ]. T h is resu lt ind ica ted that PPD S m ay in2
f luence lipop ro tein cho lestero l m etabo lism and an2
t iox idat ive act ivity. T herefo r the effect of PPD S on
to ta l cho lestero l ( TC ) , lipop ro tein cho lestero l
m etabo lism , and an t iox idat ive act ivity in experi2
m en tal hyperlip idem ia ra ts w ill be ob served and
compared w ith vitam in C in th is paper.
1　M a ter ia ls and m ethods
111　A n im als. M ale W istar ra ts w eigh ing 200—
240 g w h ich w ere supp lied by Experim en ta lA n im al
Cen ter of J ilin U n iversity w ere u sed in all experi2
m en ts. T hey w ere hou sed under a con tro lled ligh tö
dark cycle and had free access to tap w ater.
112　D rugs and reagen ts. PPD S w as p rovided by
D epartm en t of N atu ra l M edicam en t Chem istry,
Co llege of Chem istry, J ilin U n iversity. V itam in C
w as the p roduct of J ilin H enghe Pharm aceu t ica l
Co. L td. lip id perox idat ion (L PO ) and superox ide
dism u tase ( SOD ) reagen t boxes w ere pu rchased
from In st itu te of J iancheng B io techno logy, N an2
jing, Ch ina. P ro stag landin I2 R IA k it and T h rom 2
boxane A 2 R IA k it w ere pu rchased from In st itu te
of Dongya Imm uno techno logy, Beijing, Ch ina.
113　P repara t ion of hyperlip idm ia model. H yper2
lip idem ia model w as conducted acco rd ing to p revi2
ou sly described techn iques[8 ]. T he ra ts w ere fed by
hyperlip idem ia feed con ta in ing cho lestero l ( 2% ) ,
p ropylth iou racil (0. 2% ) , sodium cho la te (0. 3% ) ,
fa t ( 7. 5% ) and o rdinary feed ( 90% ) at 6: 00—
7: 00 pm fo r 12 days.
114　Experim en ta lm ethods. T he an im als w ere as2
signed to the fo llow ing experim en ta l group s: group
1, ra ts w ith the o rd inary feed w ere trea ted fo r 12
days w ith no rm al sa line ( 2 mL ökg, ip ) (no rm al
con tro l group , N C) ; group 2, ra ts w ith hyperlip i2
dem ia feed w ere trea ted fo r 12 days w ith no rm al
sa line (2 mL ökg, ip ) (model con tro l group , M C) ;
group s 3—5, ra ts w ith hyperlip idem ia feed w ere
trea ted fo r 12 days w ith PPD S (25, 50, 100 m gö
kg, ip ) ; group 6, ra ts w ith hyperlip idem ia feed
w ere trea ted fo r 12 days w ith vitam in C (400 m gö
kg, ig). A fter 24 hou rs of the last adm in ist ra t ion
the ra ts w ere anaesthet ized ( sodium pen tobarb ita l
30 m gökg ip ). B lood ( 7 mL ) w as co llected
th rough ao rta abdom inalis and among them 3 mL
w as cen trifuged fo r the serum. T rig lyceride (T G) ,
TC, h igh den sity lipop ro tein cho lestero l (HDL 2c) ,
low den sity lipop ro tein cho lestero l (LDL 2c) , L PO
con ten ts and SOD act ivity w ere determ ined acco rd2
ing to the m ethod of reagen t box. B lood (4 mL )
w as an t icoagu la ted by heparin, among them 1 mL
w as pu t in LBY2N 6A self2clean ing ro ta to ry vis2
com eter and b lood visco sit ies ( 10ös, 40ös, and
120ös) w ere m easu red. T he o ther w as cen trifuged
3 000 röm in fo r 10 m in and the p lasm a w as anal2
ysed fo r p ro stag landin I2 (PG I2 ) and th rom boxane
A 2 (TXA 2) levels w ith R IA m ethod. H alf liver w as
pu t in 10% fo rm alin and dyed in o rder to ob serve
the accum u lat ion of fa t. A no ther half liver w as
m easu red fo r L PO and SOD.
115　D ata analysis. A ll the resu lts w ere exp ressed
as x ±s. Sta t ist ica l analysis w as perfo rm ed in the
paired and unpaired studen t’s t2test. Comparison
among m u lt ip le group s w as m ade by analysis of
variance (ANOVA ).
2　Results
211 　 Effects of PPD S on the b lood lip id m eta2
bo lism of hyperlip idem ia ra ts. In the group ofM C,
the data of TC, T G, LDL 2c, TCöHDL 2c and
LDL 2cöHDL 2c in the serum are sign if ican t ly h igher
than tho se in the group of N C (P < 0105 o r P <
01001) ; the data of HDL 2c, how ever, decreased
rem arkab ly (P < 0105) , ind ica t ing that the model
of hyperlip idem ia is set up successfu lly. T he value
of serum T G, TC, LDL 2c, TCöHDL 2c, and LDL 2
cöHDL 2c in the group given by PPD S of 25, 50,
and 100 m gökg are low er than tho se in the group
of M C sign if ican t ly (P < 0105, P < 0101 o r P <
·714·中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 4 期 2004 年 4 月
01001) , respect ively, and HDL 2c in serum is in2
creased rem arkab ly in the group given by PPD S
(P < 0105 o r P < 0101). Compared w ith the data
of vitam in C, the effect of PPD S on p reserving the
b lood lip id m etabo lism of hyperlip idem ia ra ts is as
st rong as that of vitam in C (T ab le 1).
212 　 Effect of PPD S on the L PO and SOD of
serum and liver of hyperlip idem ia ra ts. It can be
seen that the increase of L PO in serum and liver
(P < 0105 o r P < 0101) , w ith the decrease of SOD
(P < 0105 o r P < 0101) , in the group of M C re2
veals that free2rad ica l2induced dam ages occu r in
the hyperlip idem ia ra ts. T he group s given by
PPD S (50, 100 m gökg) decrease the L PO in the
serum and liver, m eanw h ile, increase the SOD ac2
t ivity sign if ican t ly. T h is funct ion is the sam e as
that of vitam in C (T ab le 2).
213　Effect of PPD S on the b lood visco sity of hy2
Table 1　Effect of PPD S on blood l ip id metabol ism in hyperl ip idem ia rats (x±s, n= 10)
Group s
Do sageö(m g·kg- 1) T Gö(mmo l·L - 1) TCö(mmo l·L - 1) LDL 2cö(mmo l·L - 1) HDL 2cö(mmo l·L - 1) TCöHDL 2c LDL 2cöHDL 2c
N C - 0160±01243 1198±01543 3 3 4126±11913 3 1110±01383 1180±01663 3 3 3187±11323 3 3
M C - 1106±0146 7170±1187 7120±2116 0176±0122 10113±3148 9147±3125
PPD S 25 0191±0134 5187±11483 5176±2119 0189±0127 6160±11343 3 6147±21063
50 0171±01133 5112±11323 3 4167±11153 3 0198±01183 5122±11213 3 3 4176±11893 3 3
100 0164±01253 4153±11213 3 3 4134±11643 3 1102±01143 3 4144±11273 3 3 4125±11913 3 3
V itam in C 400 0165±01213 4164±11363 3 3 4130±11323 3 1100±01203 4164±11403 3 3 4130±11733 3 3
　　3 P < 0105　3 3 P < 0101　3 3 3 P < 0101 vs M C
Table 2　Effect of PPD S on L PO and SOD in hyperl ip idem ia rats (x±s, n= 10)
Group s
Do sageö(m g·kg- 1) SerumL PO ö(nmo l·L - 1) SOD ö(U ·L - 1) L iverL PO ö(nmo l·mL - 1) SOD ö(nU ·m g- 1)
N C - 6160±11543 3 46813±43123 5154±11073 9186±11933 3
M C - 8183±2151 40116±5714 6199±1134 7151±1138
PPD S 25 7187±2149 42811±4612 6159±1174 8145±2179
50 6176±11423 45419±35133 5168±11243 3 9104±11133
100 6122±11283 3 45718±41103 5159±11323 9118±11353
V itam in C 400 6120±11233 3 45415±32123 5156±11183 9111±11283
　　3 P < 0105　3 3 P < 0101 vs M C
perlip idem ia ra ts. T he b lood visco sity in the group
of M C is increased. T h is is due to the change of
b lood rheo logy in the hyperlip idem ia ra ts. Bu t the
b lood visco sit ies (10ös, 40ös, and 120ös) in the
group s given by 50 m gökg and 100 m gökg PPD S
are decreased. V itam in C, how ever, can no t influ2
ence the b lood visco sity sign if ican t ly (T ab le 3).
So , in the view of b lood rheo logy, PPD S p lays a
p ro tect ive ro le in hyperlip idem ia ra ts.
Table 3　Effect of PPD S on blood v iscosity
in hyperl ip idem ia rats (x±s, n= 10)
Group s
Do sageö(m g·kg- 1) B lood visco sity10 s- 1 40 s- 1 120 s- 1
N C - 11125±11303 4111±01873 3180±01743 3
M C - 13134±2131 5126±1116 4184±0183
PPD S 25 12126±2145 4189±1136 4125±0167
50 11141±11353 4198±019 3189±01983
100 11135±11283 4129±01673 3183±01623 3
V itam in C 400 11176±1168 4191±0182 4117±0193
　　3 P < 0105　3 3 P < 0101 vs M C
214 　Effects of PPD S on the level of PG I2 and
TXA 2 of p lasm a in hyperlip idem ia ra ts. T he low
level of PG I2, 281. 2 pgömL , and h igh level of
TXA 2, 438. 5 pgömL , in the group of M C, in par2
t icu lar, the ra t io betw een PG I2 and TXA 2, low er
than that in the group of N C, indica tes that the
hyperlip idem ia b reak s the balance betw een PG I2
and TXA 2. How ever, the PG I2 is increased and
TXA 2 is decreased sign if ican t ly by given 50 m gökg
and 10 m gökg PPD S, resu lt ing that PG I2öTXA 2 is
increased rem arkab ly. T h is funct ion of PPD S m ay
be bet ter than 400 m gökg vitam in C (T ab le 4).
215　Effect of PPD S on the fa t accum u lat ion in the
liver of hyperlip idem ia ra ts. T he slice of the sam 2
p le in the liver is dyed in o rder to ob serve the accu2
m u lat ion of fa t. R esu lts show that the denatu ra2
t ion of fa t t issue does no t take p lace in the cell of
liver in the group of N C among ten experim en ta l
·814· 中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 4 期 2004 年 4 月
Table 4　Effect of PPD S on plasma PGI2 and TXA2
in hyperl ip idem ia rats (x±s, n= 10)
Group s
Do sageö(m g·kg- 1) PG I2ö(pg·mL - 1) TXA 2ö(pg·mL - 1) PG I2öTXA 2
N C - 40715±112143 27817± 99153 1146±11133
M C - 28112± 8917 43815±15613 0164±0132
PPD S 25 32616±11817 33418±10213 0198±0142
50 38419± 98103 29613±110163 1130±01563 3
100 39318± 76163 28512± 98183 1138±01583 3
V itam in C 400 36613±10511 31819± 9712 1115±0182
　　3 P < 0105　3 3 P < 0101 vs M C
ra ts ( 0ö10). Bu t the denatu ra t ion s of fa t t issue
have been found in the group of M C among all the
experim en ta l ra ts (10ö10). To the group s given by
25, 50, 100 m gökg PPD S and the group given by
400 m gökg vitam in C, the ra t io of denatu ra t ion s of
fa t t issue and all the experim en ta l ra ts are 5ö10,
4ö10, 3ö10, and 4ö10, respect ively. T h is fact
demon stra tes that PPD S, along w ith vitam in C,
can inh ib it the fa t accum u lat ion in the liver re2
m arkab ly.
3　D iscussion
　　A large body of clin ica l evidence has accum u2
la ted in the past decade, suggest ing that free2rad i2
cal2induced perox idat ion of lip id crit ica lly con2
t ribu tes to the risk of hum an athero sclero sis. T h is
fa t ty st reak is pu rpo rted to the earliest lesion of
the athero sclero sis characterized by the accum u la2
t ion of monocyte2derived m acrophages loaded w ith
cho lesteryl esters and know n as foam cells ju st be2
low the endo thelium [9, 10 ]. T he st im u la t ion of cell
p ro lifera t ion at the early stage of a thero sclero sis,
part icu larly that of smoo th m u scle cells w h ich m ay
b reak th rough the elast ic lam ina and fo rm a m ass
of a thero sclero t ic p laque [10 ]. It has been found that
the fo rm at ion of a thero sclero sis is rela ted to the in2
rease of TC, T G, and LDL ; and the decrease of
HDL. T he ob ta ined resu lts in th is w o rk suggest
tha t PPD S can decrease the value of TC, T G, and
LDL 2c, and increase the con ten ts of HLD 2c,
demon stra t ing that PPD S m ay be good at the
tran sfer p rocess of cho lestero l from the su rround2
ing cells to the liver of hyperlip idem ia ra ts, resu lt2
ing in the decrease of the accum u lat ion of cho les2
tero l in the su rrounding cells and p ro tect arteria l
endo thelium again st the dam age of cho lestero l.
T h is funct ion of PPD S is sim ilar to vitam in C.
M o reover, the co rrela t ion betw een athero sclero sis
and free radica l induced perox idat ion of lip ids p ro2
po ses that the increases of L PO at the beginn ing
step of a thero sclero sis genera tes the ox idated2LDL
to fo rm foam cell by m acrophages. T h is leads to
the accum u lat ion and aff in ity of w h ite b lood cells
and b lood p la telet on the arteria l endo thelium. T he
decrease of L PO and increase of SOD act ivity
either in serum and liver can be given by PPD S.
So , PPD S p lays a p ro tect ive ro le in hyperlip idem ia
ra ts. T he fo rm at ion of th rom bu s is a lw ays associ2
ated w ith the unu sual balance of TXA 2 and PG I2.
T he lack of PG I2, rela ted to the decrease of the
syn thesis of PG I2 by LDL is harm fu l to the is2
chem ic heart d isease. O n the con trary, HDL can
st im u la te the arteria l endo thelium to syn thesize
PG I2 and be good at the ischem ic heart d isease.
PPD S can increase PG I2 and decrease TXA 2 re2
m arkab ly, leading to increasing the ra t io of PG I2ö
TXA 2. T h is funct ion of PPD S is bet ter than vita2
m in C. To th is po in t, PPD S m ay be a novel drug
to p ro tect hum an again st a thero sclero sis.
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·914·中草药　Ch inese T radit ional and H erbal D rugs　第 35 卷第 4 期 2004 年 4 月