Advances in Bioscience and Biotechnology, 2012, 3, 585-591 ABB
http://dx.doi.org/10.4236/abb.2012.35076 Published Online September 2012 (http://www.SciRP.org/journal/abb/)
Effects of Baicalin and Ligustrazine on airway
inflammation and remodeling and underlying
mechanism in asthmatic rats
Shi-Man Wu1,2*, Hai-Yan Wu2, Yong-Jie Wu2, Li Liu2, Ren-Ping Cai2, Yong-Jian Xu1*
1Respiratory Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Respiratory Department, The First Hospital of Shanxi Medical University, Taiyuan, China
Received 25 June 2012; revised 27 July 2012; accepted 10 August 2012
ABSTRACT
Aim: To explore the effects of Baicalin and Ligus-
trazine on airway inflammation and construction and
underlying mechanisms through the expressions of
GATA-3, IL-5, MMP-9 and TIMP-1 in asthmatic rats.
Methods: 30 Wistar rats were randomly divided
equally into five groups. Lung tissues were sliced.
WBC and Eos in lung tissue were estimated by HE
stain and the expressions of IL-5, GATA-3, MMP-9,
TIMP-1 and collagen type IV in lung tissue were ob-
served by immunohistochemistry. The airway wall
and airway smooth muscle thicknesses were meas-
ured by computed image analysis system. Results:
Compared with asthma group, EOS counts and the
expression of IL-5 and GATA-3 in the lung tissue
were significantly lower in normal controlled groups
(P < 0.05 or P < 0.01). Additionally, the thickness of
airway wall and airway smooth muscle did signifi-
cantly increase, and the expressions of collagen type
IV, MMP-9 and TIMP-1 were significantly higher in
asthma group (P < 0.05). With the intervention of
Baicalin or Ligustrazine, EOS decreased, and the
thicknesses of airway wall and airway smooth muscle
became thinner compared with asthma group. Mean-
while, the expression of collagen type IV, IL-5, GATA-
3, MMP-9 and TIMP-1 significantly decreased (P <
0.05). Airway wall thickness and collagen type IV
were associated with Eos, IL-5, TAGA-3, MMP-9,
TIMP-1 and MMP-9/TIMP-1. Conclusion: Two herbs
could diminish infiltration of EOS with inhibiting the
expressions of IL-5, and GATA-3, meanwhile, de-
crease the deposition of collagen type IV and the
thickness of the airway smooth muscle through regu-
lating MMP-9, TIMP-1 level and the balance between
MMP-9 and TIMP-1, additionally, had synergetic
effects.
Keywords: Asthma; Airway Remodeling; Airway
Inflammation; Baicalin; Ligustrazine
1. INTRODUCTION
Asthma is a chronic airway inflammatory disease char-
acterized by airway remodeling and reversible airflow
obstruction and involved the infiltrations of eosinophiles
(EOS), mast cells, T lymphocytes and cytokines. Airway
inflammation and remodeling are two important patho-
physiologic processes of asthma. The airway tissue in-
jury and repair from acute and chronic airway inflamma-
tion resulted in airway remodeling, which was a main
cause of irreversible airflow obstruction and a factor that
made it difficulty to treat the patients with asthma. In
addition, airway remodeling aggravated airway inflam-
mation in asthma, vice versa, in this way, those two
pathological processes were impacted each other [1]. In
asthmatic patients, EOS is a crucial effect cell for the
particular inflammation in airway mucous membrane,
even so, IL-5 plays an essential role in the inflammation,
for IL-5 could regulate EOS function through GATA-3
known as a transcription factor in TH2 lymphocytes, and
IL-5 makes EOS recruiting, activating, chemotaxis in the
inflammation site [2]. Many components involved in air-
way remodeling, including disorder of Extra cellular
matrix (ECM) degradation and deposition, hyperplasia of
smooth muscle in asthma. Matrix metalloproteinases
were main limited enzymes to regulate ECM metabolism
and influenced ECM deposition and hyperplasia of
smooth muscle [1]. So far, there has been no efficient
approach to treat or cure airway remodeling in asthma.
Herb is the Chinese traditional medicine, and plays the
peculiar parts in preventing and treating the patients with
asthma. Though herb had little side effect in treating dis-
eases, refining herb was so difficult. This experiment
chose two herbs (Baicalin and Ligustrazine) refined, and
observed the infiltration of EOS, the expressions of IL-5
*Corresponding authors.

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 586
and GATA-3, airway construction, thickness of smooth
muscle, the expressions of collagen type IV, MMP-9 and
TIMP-1 in rat model with asthma. Through the study, we
explore those herbs’ effects on airway inflammation and
airway remodeling and underlying mechanism in asthma.
2. MATERIALS AND METHODS
2.1. Animals
Thirty healthy male wistar rats (weighing 200 ± 20 g)
were from the animal center of Shanxi Medical Univer-
sity. They were kept in clean environment, and room
temperature and humidity were set at 22˚C - 25˚C and
40% - 70% respectively and the animals were provided
food and tap water. 30 health male wistar rats were ran-
domly divided equally into five groups: controlled group,
asthma group, Baicalin group, Ligustrazine group and
Baicalin added with Ligustrazine group, 6 rats each
group. All animal experimental procedures were per-
formed under the guideline of Shanxi Medical University
Animal Experiment. All animal experimentations were
approved by Shanxi Association for Laboratory Animal
Science, Taiyuan, China.
2.2. Reagents, Apparatus and Medicines
Ovalbumin (OVA) was bought from Sigma Company.
Multiple cloning antibodies of GATA-3, IL-5, Matrix
metalloproteinase-9 (MMP-9), Tissue inhibitor of metal-
loproteinase-1 (HIMP-1), collagen type IV, SABC and
DAB reagents boxes were bought from Boster Biological
Technology Co. Ltd., Wuhan, China. Injection Baicalin
were from Chengtu Master’s Limited Company of Bio-
science and Biotechnology (Chentu, China), and its mo-
lecular formula was C8H12N2·HCl·2H2O, and its mo-
lecular weight was 208.69 (HPLC ≥ 98%, 20 mg each
ampoule). Injection Ligustrazine was from Yongkang
Pharmic Limited Company (Beijing, China), and its mo-
lecular formula was C21H18O11 . Its molecular weight was
446.36 (40 mg each ampoule). 980 ultrasonic atomizer
was bought from Iatrical Equipment Company limited.
Computed image analysis system was provided by The
Pathological Department of Shanxi Medical University
(Taiyuan, China).
2.3. Asthmatic Model and Intervention of
Baicalin and Ligustrazine
Referred to Holgate’s method, rats were immunized in-
traperitoneally (i.p.) with 1 ml 10% OVA (Sigma com-
pany) mixed with Aluminum hydroxide 200 mg on day 1
and boosted in the same way on day 8. On day 14 - 42,
rats received an intranasal (i.n.) challenge with 1% OVA
for 30 min once a day.
Intervention groups: Baicalin group: on day 14 - 42,
the rats were injected intraperitoneally with Baicalin
injection 5 mg every day within half an hour before the
challenge.
Ligustrazine group: during the same period, the rats
were injected intraperitoneally with Ligustrazine injec-
tion 5 mg. and Baicalin added with Ligustrazine group:
the rats were injected intraperitoneally with Ligustrazine
injection 2.5 mg and Baicalin injection 2.5 mg respec-
tively.
Controlled group: the rats were immunized with iso-
tonic brine replaced 1% OVA. It was the mark of asth-
matic model then the rats had dyspnea, lip’s cyanosis,
abdominal rigidity, nodded breathing, lack of stability
and stiffness.
2.4. Pulmonary Tissues Collecting and
Processing
On 42 day, all animals were sacrificed within 24 hours
after the last challenge. Lungs were excised from rats,
and the right lobe was fixed by 4% paraformaldehyde,
dehydrated using series of graded ethanol. Tissues were
embedded in paraffin, and sliced as 5 μm section.
2.5. Airway Wall and Smooth Muscle Thickness
Measuring and EOS Counting
Slides were stained with H&E and their pathological
findings were observed. Ten different high power objec-
tive visual fields were chosen at random under the mi-
croscope, and EOS were counted. On the airway with
diameter 200 ± 10 μm, the thicknesses of the airway wall
and smooth muscle were measured by using computed
image analysis system.
2.6. MMP-9, TIMP-1, GATA, IL-5 and
Collagen IV Half-Quality Assay by
Immunohistochemistry
SABC method: slides were de-waxed, and the endoge-
nous peroxidase was inactivated with 3% H2O2. The an-
tigens were repaired by microwave. After the addition of
the first antibody of MMP-9, TIMP-1, GATA, IL-5 and
collagen IV, the sections were left overnight in working
liquid wet box at 4˚C, rinsed with PBS, made to react
with the second biotinized antibody for 30 min at 37˚C,
disposed for 30 min at 37˚C with streptomycintropin
labeled with horseradish peroxidase. After rinsing, the
sections were visualized with diamidobianilin (DAB),
re-stained with haematoxylin, dehydrated, mounted and
observed. PSA replaced the first antibodies in negative
control group. Ten different high power objective visual
fields were chosen at random under the microscope, and
the sections were analyzed by using computed image
analytical system. Criteria: negative as no color, weak

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 587
positive as wheat color, positive as yellow, strong posi-
tive as brown.
2.7. Statistical Analysis
All data were presented as mean ± standard deviation
(SD). The results were compared by one way analysis of
variance (AVONA). The differences between groups
were analyzed with LSD method. Multiple Liner regres-
sion analysis was employed to analyze the relationship
among the parameters (stepwise). SPSS 11.0 software
package was used for the evaluation of the statistical
significance of the data. Differences were considered
significant at P < 0.05.
3. RESULTS
3.1. Pathomorphological Changes
There were no inflammation changes in controlled group,
however, there were smooth muscle hypertrophy and
hyperplasia, thickened basement membrane and airway
wall, infiltration of bronchial and parabronchial tissue
with lymphocytes and eosinophils, increased plica mu-
cosa, desquamation of epithelium and the narrow of air-
way lumen in asthma group. In addition, there were less
inflammation in Ba icalin, Ligustrazine group and Bai-
calin added with Ligustrazine group than those in asthma
group (Figures 1-5).
3.2. The Ratio of Airway Wall Luminal to Outer
Diameters, the Thicknesses of Smooth
Muscle and Collagen Type IV (Table 1)
The thicknesses of airway wall and smooth muscle were
Figure 1. There was no significant inflammation in controlled
group, including no infiltration of bronchial and parabronchial
tissues with inflammation cell such as eosinophiles, monocytes
and lymphocyte, no smooth muscle hypertrophy and hyperpla-
sia, thickened basement membrane, mucus plug, and desqua-
mation of epithelia in airway.
Figure 2. Airway inflammation was found in asth-
matic group, mainly included smooth muscle hyper-
trophy and hyperplasia, thickened basement member,
oedematous submucosa with infiltration of granulo-
cytes, hyperplasia of mucus glands, desquamation of
epithelia, and mucus plug.
Figure 3. Mild airway inflammation was found in Bai-
calin group, included a few of inflammation cells, no or a
little of smooth muscle hypertrophy and hyperplasia, and
thickened basement member and airway.
Figure 4. Light airway inflammation was found in
Ligustrazine group, a few of granulocytes infiltrated
submucosa, there was no thickened basement mem-
ber and airway.

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 588
than those in Baicalin added with Ligustrazine group;
furthermore, collagen IV was higher in asthma group
than those in the other groups, as illustrated in Table 1.
3.3. EOS Counts, the Expression of GATA-3
and IL-5 in Lung Tissues (Table 2)
EOS count was higher in asthma group than those in the
other groups, and EOS count was lower in controlled
group than those in the other groups, as also, GATA-3
and IL-5 expressions in lung tissues were higher in asthma
group than in the other groups (Table 2).
3.4. The Expressions of MMP-9 and TIMP-1 and
MMP-9/TIMP-1 in Lung Tissues (Table 3)
Figure 5. No significant inflammation was found in
Baicalin added with Ligustrazine group; there was no
significant difference in pathological changes, com-
pared with the controlled group.
The expressions of MMP-9 and TIMP-1 in lung tissues
were higher in asthma group than those in the other
groups. MMP-9/TIMP-1 was normal in controlled group
and Ba icalin added with Ligustrazine group, but it was
ot normal in the other groups (Table 3).
thicker in asthma group than those in the other groups,
and were thicker in Baicalin and Ligustrazine group n
Table 1. The ratio of airway wall luminal to outer diameters, the thicknesses of smooth muscle and collagen type IV.
Groups n
Ratio of luminal to
outer airway diameter
Thickness of smooth
muscle (μm) Collagen IV
Controlled 6 0.81 ± 0.04 10.39 ± 0.21 51.76 ± 0.22
Asthma 6 0.63 ± 0.04▲ 19.83 ± 0.57▲ 54.32 ± 1.04▲
Baicalin 6 0.75 ± 0.03▲△● 11.52 ± 0.27▲△○ 53.31 ± 0.58△
Ligustrazine 6 0.77 ± 0.03▲△ 11.33 ± 0.36▲△○ 52.67 ± 0.18△
Baicalin added with Ligustrazine 6 0.74 ± 0.05▲△● 10.69 ± 0.28△ 51.92 ± 0.18△
Compared with controlled group, ▲P < 0.05, compared with asthma group, △P < 0.05, compared with Ligustrazine group, ●P < 0.05, compared with Baicalin
added with Ligustrazine group, ○P < 0.05.
Table 2. EOS counts, the expression of GATA-3 and IL-5 in lung tissues.
Groups N EOS (number/mm2) GATA-3 IL-5
Controlled 6 2.70 ± 0.43 0.083 ± 0.016 0.068 ± 0.019
Asthma 6 31.17 ± 0.83▲ 0.347 ± 0.015▲ 0.330 ± 0.019▲
Baicalin 6 16.58 ± 3.18▲△ 0.294 ± 0.033▲△ 0.261 ± 0.014
Ligustrazine 6 14.07 ± 0.84▲△＃ 0.192 ± 0.017▲△＃ 0.187 ± 0.020
Baicalin added with Ligustrazine 6 6.83 ± 0.98▲△＃＊ 0.165 ± 0.016▲△＃＊ 0.137 ± 0.021△
Compared with controlled group, ▲P < 0.000, compared with asthma group, △P < 0.000, compared with Baicalin group, ＃P < 0.01, compared with Ligustrazine
group, ＊P < 0.000.
Table 3. The expressions of MMP-9 and TIMP-1 and MMP-9/TIMP-1 in lung tissues.
Groups N MMP-9 TIMP-1 MMP-9/TIMP-1
Controlled 6 53.51 ± 0.25 52.84 ± 0.25 1.01 ± 0.01
Asthma 6 54.99 ± 0.83▲ 60.24 ± 3.02▲ 0.92 ± 0.11▲
Baicalin 6 53.22 ± 0.27△ 54.03 ± 0.69△ 0.99 ± 0.02
Ligustrazine 6 52.70 ± 0.49△ 54.18 ± 1.03△ 0.97 ± 0.03
Baicalin added with Ligustrazine 6 53.31 ± 0.18△ 52.41 ± 0.41△ 1.02 ± 0.02△
Compared with controlled group, ▲P < 0.02, compared with asthma group, △P < 0.01.

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 589
3.5. Multiple Liner Regression Analysis for EOS,
Thickness of Smooth Muscle and Collagen
IV (Multiple Liner Regression Equation)
EOS = 96.625IL-5 + 0.982MMP-9 – 57 .2 38
Regression coefficients is 0.957 P < 0.000
Thickness of smooth muscle = –2.639MMP-9
+ 2.985TIMP-1 + 185.661MMP-9/TIPM-1
– 0.4collagen IV + 0.39E OS
– 9.468GATA-3 – 174.207
Regression coefficients is 0.966 P < 0.000
CollagenIV = –1.113MMP-9 + 1.150TIMP-1
+ 67.097MMP-9/TIPM-1 – 2.9EOS
– 15.08GATA-3 + 26.432IL-5 – 17.8 8 3
Regression coefficients is 0.771 P < 0.001
4. DISCUSSION
Asthama is a serious global disease that cannot be cured
effectively so far. Both inhaled glucocorticosteroids and
β2-agonists are considered as two effective medicines to
treat asthma. However, the shortcomings brought by
them cannot be ignored. For example, both two medi-
cines have side effects and it is still not clear that they
can improve the airway remodeling. Herb, as the tradi-
tional Chinese medicine, has significant advantages such
as little side effects and more focuses on the balance be-
tween location and the whole body. But the deficiency of
hard to extract is the main obstruction of putting herb
into practice. However, Baicalin and Lingustrazine have
the feature of extracting easily which are not shared by
most of the herbs. The following is going to discuss how
the two medicines control the airway inflammation and
improve airway remodeling.
Bronchial asthma is an allergic disease characterized
with airway inflammation, airway remodeling and airway
hyperresponsiveness. Chronic airway inflammation was
considered as the essential of asthma, and EOS played an
important role in chronic airway inflammation which was
associated with asthma severeness [3]. In addition, IL-5
played a key part in activating EOS and regulating EOS
function, and could specifically induce EOS and make
EOS growing, differentiating and having activities [4].
Airway remodeling of bronchial asthma involved the
subepithelial collagen deposition, thickened basement
membrane and smooth muscle hypertrophy or hyperplasia
in the biopsy of bronchial mucosa in patients with asthma.
Airway structure change and airflow obstruction could
not be improved through anti-inflammation medication
and bronchodilator so it resulted in airway remodeling
which aggravated airway narrow, airflow resistance, and
airway hyperresponsiveness [5].
The extracellular matrix (ECM) in the bronchial wall
was recently reported to be an important component in
the maintenance of histological homeostasis of airway
tract by balancing synthesis and degradation of the struc-
tural component of the composition. Balance between
MMPs and TIMPs is a determinant to maintain the bal-
ance between synthesis and degradation of ECM [6].
MMP-9 and TIMP-1 are main members in MMPs and
TIMPs families respectively. MMP-9 could degrade ECM,
and TIMP-1 is the physiological inhibitor of MMP-9.
Normal cells secret MMP-9 and TIMP-1 in the ratio of 1
to 1, and they combined dissoluble non-covalence with
each other, which is irreversible and stable. In addition,
the research showed that the balance between MMP-9
and TIMP-1 was associated with airway remodeling in
asthma [6].
Baicalin is one kind of herbs, and acts as anti-in-
flammation and against allergy. The reports found that
Baicalin could decrease the EOS count in BALF, sputum
and blood and WBC count in BALF in sensitized Guinea
pig [7]. Ligustrazine is a herb too, it can improve circula-
tion of blood and anticoagulation, and treated the patients
with COPD, cardiac-encephalic vascular diseases, throm-
boembolism disease [8]. A few reports represented the
two herbs could treat airway inflammation and remodel-
ing in patients with asthma.
This experiment found that the ratio of luminal to
outer airway diameter was fewer in asthma group than in
the other groups; meanwhile, the thicknesses of smooth
muscle and the expression of collagen IV were higher in
asthma group than in the other groups. The intervention
with Ba icalin and Ligustrazine made the thicknesses of
smooth muscle and the expression of collagen IV de-
creased, and ratio of luminal to outer airway diameter
increased. Furthermore, the thickness of smooth muscle
was thinner in Baicalin added with Ligustrazine group
than in Baicalin group and Ligustrazine group, which
proved that Baicalin and Ligustrazine had a synergetic
effect on ameliorating the thickness of smooth muscle.
This study proved that two herbs reduced airway in-
flammation (decreased Eosinophil infiltration of airway)
through inhibiting expressiones of GATA-3 and IL-5.
The experiment results found that EOS, GATA-3 and
IL-5 were higher in asthma group than in the other
groups. GATA-3 and EOS were higher in Baicalin and
Ligustrazine groups than in Baicalin added with Ligus-
trazine group, and IL-5 was higher in Baicalin group
than in Baicalin added with Ligustrazine group. The re-
cent research showed that GATA-3 was a specific tran-
scription factor of TH2 lymphocyte, and induced TH2
lymphocyte to secrete cytokine. Inhibiting the expression
of GATA-3 can decrease the inflammation of airway led
by TH2 lymphocyte [9,10]. These results did also con-
firm that Baicalin and Ligustrazine could decrease the
Eosinophil infiltration of airway by inhibiting the ex-
pressiones of GATA-3 and IL-5. In addition, Baicalin
added with Ligustrazine group excelled Baicalin and

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 590
Ligustrazine groups at decreasing EOS infiltration and
the expressions of GATA-3 and IL-5. Two herbs had
synergetic effect.
This experiment showed that the expressions of MMP-9
and TIMP-1 in the airway wall of rats were higher in
asthma group than in the other groups, and the ratio of
MMP-9/TIMP-1 was abnormal in asthma group, and it
was significantly lower than in both controlled group and
Baicalin added with Ligustrazine groups. The ratio of
MMP-9/TIMP-1 was normalized in Baicalin added with
Ligustrazine group. However, the ratio of MMP-9/
TIMP-1 in Baicalin group and Ligustrazine group was
not significant compared with asthma group, so the in-
tervention of Baicalin added with Ligustrazine could
have a synergetic effect in regulating the ratio of MMP-
9/TIMP-1.
Studies showed that MMP-9, TIMP-1 and MMP-9/
TIMP-1 played crucial roles in airway remodeling [8,9].
To understand underlying mechanism of airway in-
flammation and remodeling, multiple liner regression
analysis was made. ESO infiltration of airway was pre-
sented as the characteristic of airway inflammation, and
the thickness of smooth muscle and the content of colla-
gen IV were presented as the marks of airway remodel-
ing. Furthermore, their metabolism was influenced with
airway inflammation and remodeling cytokines. Multiple
liner regression analysis found the positive correlation
between EOS and IL-5 and MMP-9, which showed that
airway inflammation cytokine (IL-5) was associated with
EOS infiltration of airway, in addition, EOS increasing
with higher expression of MMP-9 proved airway in-
flammation associated with ECM degraded. There were
the positive correlations between the thickness of smooth
muscle and TIMP-1, MMP-9/TIMP-1 and EOS, however,
and the negative correlation between the thicknesses of
smooth muscle and MMP-9, collagen IV, and GATA-3,
meanwhile, the positive correlation between the expres-
sions of collagen IV and TIMP-1, MMP-9/TIMP-1, IL-5,
nevertheless, the negative correlation between the ex-
pressions of collagen IV and MMP-9. Those results
showed that the higher expression of TIMP-1 and the
abnormal ratios of MMP-9/TIMP-1 increased the thick-
ness of smooth muscle and the expression of collagen IV,
however, the higher expression of MMP-9 decreased
them. The result proved that MMP-9 degraded ECM, and
TIMP-1 inhibited activity of MMP-9. In addition, these
results also proved that airway inflammation (EOS infil-
tration) induced higher expression of MMP-9, then the
expression of TIMP-1 did compensative increased, so
that MMP-9/TIMP-1 kept from unbalance to balance. In
same way, repeated airway inflammation and asthma
exacerbation made MMP-9/TIMP-1 unbalance and bal-
ance in turn. Finally, these pathological changes resulted
in the decompensation of collagen (deposition of colla-
gen IV), the hypertrophy of smooth muscle and the
changes of airway structure, teamed airway remodeling.
Those results were similar to Xu’s [11] and Hoshino’s
[12] ones. The results manifested that EOS infiltration of
airway, the thickness of smooth muscle and the content
of collagen IV played an important part in airway in-
flammation, maintaining airway structure and airway
remodeling respectively. With the intervention of Bai-
calin and Ligustrazine, the expressions of MMP-9 and
TIMP-1 were decreased, and MMP-9/TIMP-1 tended to
be normal. In addition, MMP-9/TIMP-1 in Baicalin
added with Ligustrazine group was not significant com-
pared with controlled group, but significant compared
with asthma group. However, MMP-9/TIMP-1 in both
Baicalin group and Ligustrazine group was not signifi-
cant compared with asthma group, so the result proved
that Baicalin and Ligustrazine had synergetic effect on
regulating MMP-9/TIMP-1.
In summary, the results found that EOS infiltration in
airway in asthma group was more than in the other
groups; smooth muscle thickness in asthma group was
thicker than in the other groups; the expression of colla-
gen IV in asthma group was higher than in the other
groups. Baicalin and Ligustrazine could inhibite airway
inflammation, decrease smooth muscle thickness, dimin-
ish the deposition of collagen IV and increase the ratio of
luminal to outer airway diameter through regulating air-
way inflammation cytokine (IL-5, GATA-3), infiltration
of EOS and airway remodeling cytokine (MMP-9, TIMP-
1 and MMP-9/TIMP-1). Furthermore, Baicalin and
Ligustrazine had synergetic effect on treating asthma,
especially airway remodeling of asthma, and both herbs
will be the effective medicines for treating asthma in
future.
5. CONCLUSION
Airway inflammation and airway wall remodeling were
two important aspects in asthma, and they were influ-
enced by each other. Eos counts and the expression of
IL-5 and GATA-3 in the lung tissues in asthma group
were significantly higher than the other groups; mean-
while, the expressions of MMP-9 and TIMP-1 signifi-
cantly were higher too. Additionally, the thicknesses of
airway wall and airway smooth muscle in asthma group
significantly increased. After intervention with Baica lin
or Ligustrazine, the thicknesses of airway wall and air-
way smooth muscle became thinner than those in asthma
group, at the same time, the expression of MMP-9 and
TIMP-1 significantly decreased. Smooth muscle thick-
ness and collagen type IV were associated with EOS,
IL-5, TAGA-3, MMP-9, TIMP-1 and MMP-9/TIMP-1.
Two herbs could inhibit the expressions of IL-5 and
GATA-3 and the infiltration of EOS and decrease the

S.-M. Wu et al. / Advances in Bioscience and Biotechnology 3 (2012) 585-591 591
deposition of collagen type IV and reduce the airway
smooth muscle thickness through regulating MMP-9 and
TIMP-1 level and influencing the balance between MMP-
9 and TIMP-1, and had synergetic effect. This will pro-
vide new therapeutic way to asthmatic patients.
6. ACKNOWLEDGEMENTS
We wish to thank the Shanxi Science and Technology Department for
the funding of the study. We are also grateful to professor Jun-mai
Zhao for help in the computed image analysis.
Foundation: International Cooperative Project of Shanxi Province,
China, 30370608.
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