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Dong
Shang, Feng-Lin Guan, Pei-Yu Jin, Hai-Long Chen, Jian-Hua Cui, 1Second
Department of General Surgery, 2Department of Endoscopy,
First Affiliated Hospital of Dalian Medical University, Dalian
116011, Liaoning Province, China
Dr. Dong Shang, male, born on February 5, 1971 in Liaoyang City,
Liaoning Province, and graduated from Dalian Medical University as a
postgraduate in 1997, attending Dalian Medical University for MD,
specialized in treating the biliary tract and pancreas diseases with
integrated traditional Chinese and modern medicine, having 4 papers
published.
Project supported by the National Natural Science Foundation of
China, No.38970871.
Correspondence to: Dr. Dong Shang, Second Department of
General Surgery, First Affiliated Hospital of Dalian Medical
University, Dalian 116011, Liaoning Province, China
Telephone:
+86-411-3635963 ext 3130,
Fax. +86-411-3635963
Received: 1998-05-21
Subject
headings: cholangitis; endotoxemia;
sphincterotomy; endoscopy; Yin Chen Hao Cheng Qi decoction
Shang D, Guan FL, Jin PY, Chen HL, Cui JH. Effect of combined
therapy of Yinchenhao Chengqi decoction and endoscopic
sphincterotomy for endotoxemia in acute cholangitis.World J
Gastroenterol, 1998;4(5):443-445
Abstract
AIM: To evaluate the therapeutic mechanism of Yinchenhao
Chengqi (YCHCQ)decoction (containing mainly Herba Artemisia
capillaris) combined with endoscopic sphincterotomy (EST) for
endotoxemia (ETM) in acute cholangitis.
METHODS: Twenty-one cases of acute cholangitis with ETM were
divided randomly into two groups: group A, 10 patients treated with
YCHCQ decoction combined with EST, group B,11 patients treated with
EST. The incidence rate of ETM, plasmic ET, serum superoxide
dismutase (SOD) activity, malonyldialdehyde (MDA), complement C3 and
C-reactive protein (CRP) were studied respectively.
RESULTS: The ET level of group A (35.92ng/L±8.30ng/L) was
significantly reduced after 7 days of treatment (P<0.05)
in contrast to that of group B (47.8ng/L±11.62ng/L), so did the
level of MDA and CRP. But the SOD activity and C3 level in group A
increased significantly (P<0.05).
CONCLUSION: YCHCQ decoction combined with EST had a
beneficial effect for ETM in acute cholangitis.
INTRODUCTION
Endotoxemia (ETM) is one of the most important physiopathologic
causes of acute cholangitis and it is the trigger of cytokines and
inflammatory factors. In recent studies it has been found that
Yinchenhao Chengqi (YCHCQ) decoction has a beneficial effect on ETM
in acute cholangitis. With the development of endoscopic surgery,
endoscopic sphincterotomy (EST) has become an effective replacement
for some operations in the treatment of acute cholangitis[1].
The effect of YCHCQ decoction combined with EST on ET, oxygen free
radical and complement C3 was observed in order to find
out its therapeutic mechanism.
MATERIALS AND METHODS
Clinical materials
Twenty-one cases of acute cholangitis with endotoxemia were divided
randomly into two groups: group A, 10 patients (6 males and 4
females) treated with YCHCQ decoction and EST; and group B, 11
patients (6 males, 5 females) treated with EST
(Tables 1,2).
Table 1 Disease composition of acute cholangitis
|
Group
|
No.
of patients
|
Common
bile duct stones (%)
|
Benign
stenosis of Oddi′s
sphincter (%)
|
Biliary
ascariasis (%)
|
|
Group
B
|
11
|
6(55)
|
4(36)
|
1(
9)
|
|
Group
A
|
10
|
6(60)
|
3(30)
|
1(10)
|
Table
2 Comparison of general condition
|
Group
|
No.
of
patients
|
WBC
in peripheral blood (109/L)
|
Percent
of
neutrophil cell
|
Temperature
(℃)
|
Age
(years)
|
|
Group
B
|
11
|
15.47±6.83
|
0.85±0.08
|
38.92±1.32
|
52.43±13.61
|
|
Group
A
|
10
|
15.36±7.26
|
0.83±0.09
|
38.87±1.24
|
56.21±14.17
|
|
P
|
|
>0.05
|
>0.05
|
>0.05
|
>0.05
|
Methods
EST treatment EST was performed on the patients with benign
stenosis of Oddi′s
sphincter. Besides EST, stone extraction using Dormia basket,
retrieval balloon or mechanical lithotriptor was also followed in
the patients with common bile duct stones, and ascaris lumbricoides
extraction using forceps was conducted in those with biliary
ascariasis.
Combined treatment of EST and YCHCQ decoction The patients in
group A took one YCHCQ decoction a day, 100mL in the morning and
100mL at night. YCHCQ dection was composed of Herba Artemisiae
capillaris 30g,Fructus Gardeniae 15g, Cortex Magnoliae Officinalis
15g, Fructus Aurantii 15g, Radix et rhizoma Rhei 15g (added later)
and Natrii Sulfas 10g (taking with hot decoction).
Assay of ET, superoxide dismutase (SOD), malonyldialdehyde (MDA),
complement C3 and C-reactive protein (CRP) in peripheral
blood Plasmic ET was measured using limulus ozo-group
development process, serum SOD was determined using xanthine oxidase
process, and MDA by the thiobarbituric acid clorimetric method. CRP
and C3 were detected with fully-automatic instruments for
biochemical analysis.
Definition of ETM ET in peripheral blood of 50 normal
volunteers was measured. The result was 32.53ng/L±10.32ng/L.
Plasmic ET of 95% normal volunteers ranged from 0ng/L to 53.84ng/L.
If it is above 54ng/L, it is defined as ETM.
Statistical analysis
The results were expressed as mean±SD.
Data were analyzed using Student′s
t test. The incidence rate of ETM was analyzed using x2
test. P value less than 0.05 was considered significant.
RESULTS
The average days of hospitalization in group A were 7 days, 9
recovered and 1 improved, and no complication occurred, while, the
average days of hospitalization of group B were 12 days, 9 recovered
and 3 improved, and complications occurred in 2 cases, including one
case of acute peritonitis, and one case of common bile duct stones
at the ampulla of Vater who underwent an operation to remove the
stones.
Effect of different treatment on ETM
In Table 3, plasmic ET level of the two groups was markedly higher
than that of the normal volunteers, and ETM occurred. On the 3rd day
after treatment, the incidence rate of ETM in group A was lowered
significantly, as compared with that before treatment. The incidence
rate of group B also decreased, but there was no significant
difference as compared with before until the 5th day after
treatment. The plasmic ET level of the two groups declined obviously
on the 3rd day, but without significant difference between the two
groups. On the 5th and 7th day, ET level was lower in group A than
in group B.
Effect of different treatment on the activity of serum SOD
Before treatment, the activity of serum SOD was lower in both groups
than normal (104.2kNU/L±18.8kNU/L). There was nosignificant
difference between the two groups, although on the 3rd and 7th day
after treatment, the activity of serum SOD in the two groups
obviously increased, that of group A being much higher than that of
group B (P<0.05).
On the 7th day, serum SOD values of group A had already turned
normal (Table 4).
Table 3 Changes of the incidence rate of ETM
|
Group
|
No.of
patients
|
Before
treatment (%)
|
After
treatment(%)
|
|
d3
|
d5
|
d7
|
|
Group
B
|
11
|
11/11(100)
|
9/11(82)
|
1/11(64)a
|
3/11(27)a
|
|
Group
A
|
10
|
10/10(100)
|
6/10(60)a
|
2/10(20)ac
|
|
aP<0.05,
comparison of intra group; cP<0.05,
comparison among groups. χ2 test.
Table 4 Changes of plasmic ET, serum SOD and MDA (mean±SD)
|
Group
|
No.of
patients
|
Before
treatment (%)
|
After
treatment(%)
|
|
d3
|
d5
|
d7
|
|
Plasmic
ET (ng/L)
|
|
Group
B
|
11
|
97.12±15.20
|
72.84±10.36a
|
62.61±10.08a
|
47.80±11.62a
|
|
Group
A
|
10
|
98.67±15.54
|
67.07±13.50a
|
48.18±11.46ac
|
35.92±8.30ac
|
|
Serum
SOD (kNU/L)
|
|
Group
B
|
11
|
62.52±8.01
|
72.38±10.52a
|
86.89±13.56a
|
|
|
Group
A
|
10
|
63.68±9.45
|
96.47±15.35ac
|
105.18±13.21ac
|
|
|
Serum
MDA (μmol/L)
|
|
Group
B
|
11
|
38.50±2.29
|
24.40±2.43a
|
12.47±1.70a
|
|
|
Group
A
|
10
|
37.32±3.80
|
6.40±1.28ac
|
4.33±1.03ac
|
|
aP<0.05,
comparison intra-group; cP<0.05,
comparison among groups. Student′s
t test.
Effect of different treatment on the level of serum MDA
It is shown in Table 4 that the level of serum MDA lowered in
various degrees in both groups after treatment. MDA level in group A
became nearly normal on the 7th day.
Effect of different treatment on the level of serum CRP
There was no difference in the CRP level between the two groups,
which was both obviously higher than the normal level before
treatment. The CRP level obviously decreased after treatment on the
3rd and 7th day. However, the CRP value in group A declined much
more significantly than that in group B (P<0.05)
(Figure 1).
Figure 1(PDF)
Changes of
serum CRP. aP<0.05,
comparison intra group; cP<0.05,
comparison among groups. Student′s
t test. A: Before treatment; B: The 3rd day after treatment;
C: The 7th day after treatment.
Effect of different treatment on serum C3
As shown in Figure 2, there was no significant difference in serum C3
of the two groups which was both lower than the normal before
treatment. However, patients treated with combined YCHCQ decoction
and EST had significantly higher serum SOD than group B.
Figure 2(PDF)
Changes of
serum C3. aP<0.05,
comparison intra group; cP<0.05,
comparison among groups. Student′s
t test. A: Before treatment; B: The 3rd day after treatment;
C: The 7th day after treatment.
DISCUSSION
Therapeutic mechanism of YCHCQ decoction on ETM in acute
cholangitis
As an antagonistic agent, YCHCQ decoction can reduce ET production
and absorption. Redix et Rhizoma Rhei and Natrii Sulfas
could get rid of abdominal mass, bacteria and ET with an effect of
“Tongligongxia” in TCM to reduce the ET. Redix et Rhizoma Rhei,
Fructus Gardeniae and Cortex Magnoliae Officinalis have a
more powerful bacteriostatic effect to reduce the production of ET
and the incidence of ETM derived from the gut[2].
Redix et Rhizoma Rhei, Herba Artemisiae Scopariae and Fructus
Gardeniae are also cholagogues, antispasmodics and
anti-inflammatory agents. They can lower the incidence rate of ETM
which resulted from bile duct obstruction because the inflammatory
bile in the bile duct flows into the intestinal tract. Some studies
have confirmed that Redix et Rhizoma Rhe has a more powerful
antagonistic effect on ET. The destroyed reticular structure of ET
by Redix et Rhizoma Rhe was observed under electron
microscope.
YCHCQ
decoction could reduce the production of oxygen free radical. ET
could activate the respiratory burst of leukocyte. A large amount of
oxygen free radicals strongly damage the histocyte, particularly the
gut barrier[3].
Peroxide, such as MDA etc, is produced because of lipid peroxidation
by oxygen free radical which could attack multiple unsaturated fatty
acid on the biological membrane[4].
YCHCQ decoction may reduce the production of peroxide MDA, increase
the activity of SOD, decrease the permeability of capillary, and
promote microcirculation. Therefore, it can reduce the production of
oxygen free radical, keep the balance of oxidation and antioxidation,
lessen the damage to the gut barrier, reduce the production and
absorption of ET, inhibit the cascade effect of ET and oxygen free
radical, stop pernicious circulation, keep the stabilization of the
internal environment, raise the ability of antioxidation and
alleviate the damage of peroxidation to organisms.
YCHCQ
decoction could enhance immunologic function, and promote the
recovery of the function of the complement system, the macrophage
system and the inactivation of ET.
Effect of combined YCHCQ decoction and EST on ETM in acute
cholangitis
This study confirms that YCHCQ decoction combined with EST had a
better therapentic effect on ETM in acute cholangitis. Its
advantages are that: EST could incise part of the papilla so as to
clear common bile duct stones with mechanical litheropsy instrument,
and to eliminate the factors of mechanical obstruction and bile duct
stenosis. On the basis of this action, the therapeutic effect of
YCHCQ decoction could be fully exerted. Thus, the most important
factors of acute cholangitis were eliminated because common bile
duct stones were successfully removed with the combined treatment.
In addition, endoscopic retrograde biliary drainage or endoscopic
nasobiliary drainage were performed after EST, in order to reduce
the pressure of the bile duct, drain the inflammatory bile, remove
the “Damp-Heat” and the mass on the abdomen, normalize secretion
and discharge the bile, reduce jaundice, and preserve the function
of the liver and the kidney.
EST
is an established non surgical method of management for patients
with acute cholangitis from biliary obstruction or various causes.
The results show that the patients undergoing EST do not require
surgical operation and rarely suffer from complications. They need
only a short time of hospitalization, experience little pain, and
obtain a rapid recovery. Also, this treatment dose not have the
limitations caused by repeated surgical operations or the conditions
of patients[5].
YCHCQ decoction could reduce or eliminate the occurrence of ETM in
acute cholangitis. With its therapeutic effect of
“Tongligongxia” and clearing away “damp heat” and
“Fuzhengquxie” in TCM, YCHCQ decoction can reduce the production
of oxygen free radical and lipid peroxidation, thus inhibiting the
production and absorption of ET.
REFERENCES
1 Boender J, Nix GA, Ridder MA, Dees J, Schutte
HE, Buuren HR et al. Endoscopic sphincterotomy and biliary drainage
in
patients with cholangitis due to
common bile duct stones.Am J Gastroenterol, 1995;90(2):233-238
2 Chen HL, Zhou JY, Guan FL, Guo PL. Clinical
study of therapeutic effect of Compound Dachengqi Tang on ETM in
obstructive jaundice.J Integr Med,
1991;11(12):724-726
3 Chen HL, Wu XZ. Cytokines and Multiple system
organ failure.Foreign Med Sci, (Sec Physiol Pathol Clin),
1995;15(4):261-264
4 Borregaard N, Miller LJ, Springer TA.
Chemoattractant-regulated mobilization of a novel intracellular
compartment in
human neutrophils. Science,
1987;237(9):1204-1206
5 Prat F, Tennenbaum R, Ponsot P, Altman C,
Pelletier G, Fritsch J et al. Endoscopic sphincterotomy in patients
with liver
cirrhosis. Gastrointest Endosc,
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