The protective effect of red ginseng pulse-activated injection (RPI) on cardiac muscle in septic shock rats

The protection of RPI on septic shock rats / Asian Journal of Traditional Medicines, 2007, 2 ( 4 )
The protective effect of red ginseng pulse-activated injection (RPI)
on cardiac muscle in septic shock rats
Ying Zhang, Xiaomian Zhou *, Fanying Meng, Yinglin Cao, Xing Tang
Shengli Teaching and Reseach Group, Shenyang Pharmaceutical University, Shenyang 110016, China
The protective effect and the possible mechanism of action of red ginseng pulse-activated injection (RPI) on cardiac muscle in septic
shock rats were studied. More than sixty healthy Wistar rats were divided randomly into six groups: a sham CLP group, a CLP
group, an RPI (17, 8.5, 4.3 g/kg) group and a positive control group (DXGXZSY). To observe the effect of RPI on blood pressure,
cardiac muscle, whole blood lactic acid levels and blood-serum NO levels in septic shock rats?cecal ligation and puncture (CLP) was
used to reproduce septic shock model. The blood pressure was decreased after the operation compared with that of the sham CLP
group. RPI elevated the blood pressure of septic shock rats and decreased the damage in cardiac muscle although at different doses.
At the same time RPI also decreased the levels of both whole blood lactic acid and blood-serum NO. Therefore, RPI can protect
cardiac muscle from septic shock in CLP rats. The mechanism of action may be related to of its ability to decrease blood-serum NO.
Key words: red ginseng pulse-activating injection; septic shock; cecal ligation and puncture; lactic acid; NO
Septic shock is a serious condition that occurs
blood lactic acid (LD) and blood-serum NO in these
when an overwhelming infection leads to low blood
septic shock rats were determined which suggested its
pressure, low blood flow, metabolic acidosis, and
possible mechanism of action.
death. The heart and the other organs may not
function properly or may fail. Mortality rates are
Materials
approximately 46 ?-82 ?[1]. The main components
of red ginseng pulse-activating injection (RPI)
Medicine
are red ginseng, ophiopogonis tuber, and Chinese
The red ginseng pulse-activating injection (2.84
magnoliavine fruit. Recent clinical studies indicate
g·mL-1) was offered by Pharmaceutics Teaching
that pulse-activating injection has the effect of
and Reseach Group of Shenyang Pharmaceutical
enhance the function of heart, rise the blood pressure,
University. The main components are red ginseng (0.5
and ameliorating the effect of microcirculation [2], so
g·mL-1), ophiopogonis tuber (1.56 g·mL-1) and Chinese
that it has become a common emergency traditional
magnoliavine fruit (0.78 g·mL-1). Danxiangguanxin
Chinese medicine treatment for septic shock. Cecal
injection (DXGXZSY, 2mL/ramus ) was offered by
ligation and puncture (CLP) was used to produce
Shanghai Zhongxi Medical limited company. LD
septic shock model. Then the effects of RPI on blood
and NO kits were offered by Nanjing Jiancheng
pressure, cardiac muscle, and the levels of whole
bioengineering institute.
Animals
* Author to whom correspondence should be addressed. Tel:
A total of 80 Wistar rats with both sex at the weight
+86-24-23986368; E-mail: zhouxiaomian2411@yahoo.com.cn

of 180–220 g were obtained from Experimental Animal
Received: 2006-10-27 Accepted: 2007-06-01
Center of Shenyang Pharmaceutical University.
154

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The protection of RPI on septic shock rats / Asian Journal of Traditional Medicines, 2007, 2 ( 4 )
Methods
convention color.
The effect of RPI on blood pressure in septic
Statistical analysis
shock rats [3-4]
Different data were analysed statistically by
Cecal ligation and puncture (CLP) was used
Students’ t-test methods.
to reproduce septic shock model [3-4]. And 60 rats,
which were still alive at the 20 hour after CLP, were
Results
randomly divided into six groups: the sham CLP
group, the CLP group, the RPI
general observation
(17, 8.5, 4.3 g·kg-1)
group and the positive control group (DXGXZSY 2
5 hours later after CLP, part of animals appeared
mL·kg-1). All the rats were anaesthetized by injection
the symptoms of dispiritment, shakes, piloerection,
of 20 %?w?ethyl carbamate at a dose of 1.2 g·kg-1
alvi profluvium, pyuria and more cantho-excreta, and
(i.p.). The blood pressure was measured respectively
the conditions became more and more serious.
before administration of different doses of drugs and
The effect of RPI on blood pressure in septic
at 10, 30, 60, 90, 120 min intervals after injection by
shock rats
RM6240CD multiple physio-signal processing system
on left arteria carotis communis.
The study reveals that the blood pressure in septic
shock rats was decreased significantly compared with
The effect of RPI on whole blood lactic acid and
that in the sham CLP group. And the animals’ blood
blood-serum NO in septic shock rats [5]
pressure was significantly increased compared with
After administration, blood samples were
that in the CLP group after administration (Table 1).
collected 120 min later and the whole blood lactic acid
The effects of RPI on whole blood lactic acid and
and blood-serum NO were determined by kits.
blood-serum NO in septic shock rats
The effect of RPI on cardiac muscle in septic
It was observed that RPI significantly reduced the
shock rats
whole blood lactic acid (LD) and blood-serum NO in
Animals were sacrificed at last, and cardiac
septic shock rats at every dose (Table 2).
muscle was collected from each animal and fixed by
The effect of RPI on cardiac muscle in septic
10 % formalin?and tested under microscope after HE
shock rats
Table 1 The effect of RPI on blood pressure in septic shock rats? x ±s, n?10?
Before
After administer (kPa)
Group
Dose
(g•kg
administer
-1)
(kPa)
10 min
30 min
60 min
90 min
120 min
Sham
-
22.50 ± 1.65
23.36 ± 1.14
24.34 ± 1.63
23.78 ± 0.99
23.44 ± 1.48
23.32 ± 1.96
model
-
16.12 ± 1.53 ## 16.42 ± 1.65 ##
16.06 ± 2.15 ##
15.48 ± 2.30 ## 15.14 ± 2.32 ##
15.83 ± 2.57 ##
RPI
17
17.43 ± 1.92 ##
21.34 ± 1.78 *
21.74 ± 1.55 **
22.40 ± 1.74 ** 22.00 ± 1.94 **
21.78 ± 1.75 **
8.5
16.43 ± 1.55 ##
19.83 ± 1.94 *
20.28 ± 2.72 *
20.50 ± 2.22 ** 20.50 ± 2.65 **
19.43 ± 2.51 **
4.3
16.39 ± 1.93 ##
19.79 ± 2.74 *
19.84 ± 2.98 *
19.72 ± 3.03 *
18.76 ± 2.82 *
19.00 ± 3.32 *
DXGXZSY
2 mL·kg-1 17.63 ± 2.07 ##
21.50 ± 1.91 *
21.67 ± 1.92 *
21.68 ± 2.54 *
20.80 ± 2.30 *
20.38 ± 2.95 *
*P < 0.05?**P < 0.01 compared with model group; ##P < 0.01 compared with Sham.
155

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The protection of RPI on septic shock rats / Asian Journal of Traditional Medicines, 2007, 2 ( 4 )
Table 2 The effects of RPI on LD and NO in septic shock
shock model was reproduced.
rats? x ±s, n?10?
Septic shock represents an important cause
of mortality among the critically ill, particularly if
Group
Dose
LD
NO
(g•kg-1)
(mmol•L-1)
(?mol•mL-1)
cardiovascular dysfunction ensues [7]. The toxins
Sham
?
2.91 ± 0.98
15.27 ± 6.27
produced by some bacteria cause the cardioblast
model
?
10.28 ± 2.00 ##
27.67 ± 10.98 ##
congestion, cutaneous dropsy, apomorphosis and
RPI
17
3.02 ± 0.84 **
12.75 ± 3.46 **
necrosis [8]. It was reported that excess NO released
8.5
6.03 ± 1.99 **
14.09 ± 3.20 **
by nitricoxide synthase (NOS) under the derivation
4.3
6.34 ± 1.58 **
25.38 ± 7.35
of endotoxin contributes to vasodilatation and cardiac
DXGXZSY
2 mL•kg-1
5.35 ± 0.54 **
25.13 ± 5.61
depression [9-10]. NO will cause the peripheral vascular
**
dilate pathologically and abnormity blood flow. The
P < 0.01 compared with model group?##P < 0.01 compared
with Sham.
bulk of blood flow into venous system without oxygen
delivery to organization, which cause hypoxia and
the level of LD increases. The increasing of LD
Under electron microscope it was observed that
may induce the depletion of organ. The CA released
the cardiac muscle fibers of sham CLP were line up in
multiplicitily by body can excite both ?-receptors and
order, and the cardiac muscle and interstitial substance
?-receptors, and induce angiospasm. The condition
had been no abnormality seen (Fig. 1). The cardiac
of anoxaemia may lead to excessive LD and acidosis,
muscles of CLP collapsed and dissolved seriously
which can induce arrhythmia, cut down the myocardial
(Fig. 2). The cardiac muscle fibers of RPI (17 g·kg-1)
contractile force and reactance of blood vessel to CA.
were line up in order, and the cardiac muscle and
And all of these conditions can aggravate the injury of
interstitial substance had been no abnormality seen
cardiac muscle [11]. The high stringent state caused by
(Fig. 3). The cardiac muscle fibers of RPI (8.5 g·kg-1)
septic shock increases the myocardial consumption of
collapsed partly (Fig. 4). The cardiac muscle fibers
oxygen, and the low blood pressure induces the blood
of RPI (4.3 g·kg-1) collapsed more seriously (Fig. 5).
flow to aeteria coronaria reduce, which cause the
The cardiac muscle fibers of the positive control group
cardiac muscle’s ischemic necrosis [12].
collapsed lightly (Fig. 6).
The main component of red ginseng in RPI
is panaxsaponin, which has the ability of increase
Discussion
the myocardial contractile force?cardiac output
It has a phenomenon of “pathological flow
and blood pressure. The study indicated that RPI
dependency on O ” with heavy patients [6]. Which
could decrease the blood-serum NO, protect the
2
means the supply of oxygen increase, and the demand
cardiac muscle, and reduce the negative inotropic
increase, either. The supply of oxygen to of LD
effect of NO. At the same time the depression of
increases. The level of whole blood LD is a good
NO could upgrade the blood pressure, increase the
indicatrix of hypoxia. Cecal ligation and organism is
hemoperfusion of cardiac muscle and retrieve the
inequacy, which will cause hypoxia. When anaerobic
anoxyaemia of cardiac muscle, simultaneously the
metabolism augments, the level puncture (CLP)
condition of acidosis was anesised. Above all, RPI
was used to reproduce septic shock model. It was
had the effect of protection on cardiac muscle in
observed that the blood pressure decreased gradually,
septic shock rats, which was possible related to the
the whole blood LD and blood-serum NO increased
depression of the whole blood LD and blood-serum
significantly and the cardiac muscle fibers collapsed
NO.
and dissolved seriously, which indicated that the septic
156

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The protection of RPI on septic shock rats / Asian Journal of Traditional Medicines, 2007, 2 ( 4 )
The protection of RPI on septic shock rats

The protection of RPI on septic shock rats
Fig. 1
Fig. 1 T
The sham CLP he sham CLP group: the card
group: the cardiac muscle fibers were iac Fig
Fig. 2 . 2 The
The CLP CLP group: the cardiac
group: the cardiac muscle fibers collapsed and
muscle
line up in order. ?×400 fibe
?
rs were line up in order. muscle fibers
dissolved seriously.?
collapsed a
×400?
nd
×400 dissolved seriously. ×400

F i g . 3 T h e R
P I (1 7 g · k g-1
) gr
oup:
the
F
ig . 4 TTh
he e R
prot P
ec Iti (8
on .5g
of ·k
RP g-1
I )
on g
sero
ptiuc ps: the
hock rats
Fig. 3 The RPI (17g·kg-1) group: the cardiac muscle fibers
Fig. 4 The RPI (8.5g·kg-1) group: the cardiac muscle fibers
card
were line up in order. ia
? c m
×400us
? cle fibers were line up cardiac muscle fibers
collapsed partly.?×400?
collapsed
in order. ×400
partly. ×400

Fig. 5 The RPI (4.3g·kg-1) group: the Fig. 6 The positive control group: the
Fig. 5 The RPI (4.3g·kg-1) group: the cardiac muscle fibers
Fig. 6 The positive control group: the cardiac muscle fibers
cardiac
collapsed more seriously.? muscle
×400?
fibers collapsed
cardiac
collapsed lightly. muscle
?×400? fibers collapsed
more seriously. ×400
lightly. ×400

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