Effect of airway remodeling on airway responsiveness in asthmatic guinea pigs

AIM: To establish a guinea pig asthma model and to evaluate the effect of airway remodeling on airway responsiveness. METHODS: The guinea pig asthma model was established by ovalbumin (OVA) sensitization and challenge repeatedly. Bronchial provocation tests were conducted through intravenous injection of acetylcholine. The airway morphologic parameters were measured by computer image analysis system. White blood cells and the differential count in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: The resistance of airway was increased significantly after 4 weeks of OVA exposure, but the increase disappeared upon prolonged exposure. After 8 weeks of OVA exposure, fiber tissue in large airway was increased, and the thickness of smooth muscle layer of small airway was enlarged, as compared with that in control animals. CONCLUSION: Airway responsiveness has changed after prolonged OVA exposure in guinea pigs. This change is related to airway remodeling.     

Role of GATA-3 in the pathogenesis of airway inflammation in a rat asthma model

AIM: To investigate the role of GATA-3 in the pathogenesis of airway inflammation in a Wistar rat asthma model. METHODS: The Wistar rat asthma model was made with conventional method and animals were divided into five groups (10 rats in each group): asthma group (A group), dexamethasone group (D group), antisense oligonucleotide group (AS group), nonsense oligonucleotide group (NS group) and normal control group (N group). Antisense, nonsense oligonucleotide were administered intranasally, and the dexamethasone was injected intraperitoneally. The airway inflammation was observed with HE staining method. The GATA-3 positive cells were stained immunohistochemically. The GATA-3 mRNA expression in pulmonary tissue was investigated with RT-PCR. The GATA-3 protein in pulmonary tissue was detected by Western blotting. RESULTS: In contrast to N group, the expression of GATA-3 mRNA, protein and the amount of inflammatory cells in pulmonary tissue in group A were increased significantly (P<0.01) and were decreased evidently in group AS and D (P<0.01). The expression of GATA-3 mRNA, protein and the amount of inflammatory cells in NS group were obviously increased compared with those in gropu AS and D (P<0.01). The expression of GATA-3 was related to the amount of eosinophils (r=0.995). CONCLUSION: GATA-3 antisense oligonucleotide blocks the expression of GATA-3 gene and the infiltration of eosinophils. GATA-3 plays an important role in the effector phase of allergic airway inflammation in a Wistar rat asthma model.     

Inhibitory effect of T-bet gene transfer on airway inflammation in a established murine allergic asthmatic model

AIM: To investigate the effect of T-bet plasmid gene transfer to airway on allergen induced airway inflammation in a murine asthmatic model. METHODS: A mouse asthma model was established by sensitization with ovalbumin (OVA). Forty C57BL/6 mice were divided into 4 groups (10 mice in each group): the normal control group (group A), the asthmatic model group (group B), the pcDNA3 plasmid group (group C), and the pcDNA3-T-bet group (group D). The animals in group B, C and D were sensitized and challenged with OVA. The animals in group A were applied with normal saline. pcDNA3 plasmid at dose of 50 μg was intranasally administered at 24 h before intranasal challenges to the mice in group C, and the 50 μg pcDNA3-T-bet plasmid for the mice in group D. Bronchial alveolar lavage fluid (BALF) was collected and lung tissues were resected at 48 h after OVA challenge for later assay. RESULTS: After administration with pcDNA3-T-bet plasmid, high level of T-bet expression at 48 h was detected in the lung tissue by Western blotting. In pcDNA3-T-bet treated asthmatic models, histological evaluation revealed the significant suppression of eosinophil peribronchial and perivascular infiltration, and reduction of epithelial damage. The numbers of eosinophils, neutrophils and lymphocytes in BALF from pcDNA3-T-bet treated mice were significantly reduced compared to those in asthmatic control group (P<0.05). The level of IL-4 in BALF was significantly decreased in pcDNA3-T-bet group compared to that in asthmatic control group (P<0.05), while the level of IFN-γ in BALF was significantly increased in pcDNA3-T-bet group. No significant change of inflammation cells and cytokines in pcDNA3 plasmid group and asthmatic control group was observed (P>0.05). CONCLUSION: Intranasal pcDNA3-T-bet plasmid transfer inhibits asthmatic airway inflammation in the murine asthmatic model, suggesting a new therapeutic strategy for allergic asthma.     

The relationship between Proto-oncogenes expression and airway inflammatory cell infiltration in asthma

AIM:To investigate the relationship between inflammatory cell infiltration and proto-oncogenes expression in asthma. METHODS:Guinea pigs were used as asthma models challenged by ovoglobulin. Dot-blot, Northern-blot and immunochemical techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Inflammatory cell infiltration was showed by pathologic study.RESULTS:c-fos and c-myc mRNA could not be detected or expressed at very low level in control group. Those were greatly increased after the animals are challenged by ovoglobulin. Immunochemical study showed that Fos, Myc, Jun and Sis expressed at low level in control group, and those were increased after the challenge. There was little inflammatory cell infiltration in control group. Lymphocyte, neutrophil and eosinophil were detected immediately after the challenge, a great number of inflammation cells could be seen after 12-24 h of the challenge. Majority of neutrophil and eosinophil were under mucosa or in epithelium in airway. CONCLUSION:Oncogenes expression had strong relationship with airway inflammation.     

Expression of IFN-γ, IL-4 and IL-17A in asthmatic mice vaccinated with BCG and HepB in neonatal period

AIM: To investigate the expression of IFN-γ, IL-4 and IL-17A in asthmatic mice vaccinated with bacillus Calmette-Guérin (BCG) and hepatitis B (HepB) in the neonatal period. METHODS: BALB/c mice were randomly divided into BGG+HepB+ovalbumin (OVA) group (B/H/O group), B/O group, H/O group, B/H group, OVA group, BCG group, HepB group and normal saline (NS) group (n=6). The mice in B/H/O group and B/H group at 0, 7 and 14 d received subcutaneous injection of 1×10⁵ CFU BCG for 3 times, while at 0 and 28 d received intramuscular injection of 1.5 μg HepB on the hindlimb twice. The mice in other groups were individually vaccinated with BCG or HepB. OVA sensitization and aerosol inhalation were performed to establish the asthma model. The lung tissues were collected for HE staining. Bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected, and the number of eosinophils (EOS) in BALF was counted. The serum levels of IFN-γ and IL-4, and the level of IL-17A in lung tissue homogenate were measured by ELISA. RESULTS: The pathological changes of the lung in OVA group, B/O group, B/H/O group and H/O group were observed. There were extensive inflammatory cell infiltration around the bronchus, and epithe-lial cell hypertrophy. Those in B/H/O group and H/O group were worse than those in OVA group, while those in B/O group was better than those in OVA group. Total BALF cell counts in B/H/O group, B/O group and H/O group were decreased (P<0.05) as compared with OVA group. The BALF EOS count in B/H/O group was higher than that in B/H group, that in B/O group was higher than that in BCG group, and that in H/O group was higher than that in HepB groups (P<0.05). Compared with H/O group, OVA group and NS group, the serum IFN-γ/IL-4 ratio in HepB group was increased (P<0.05), and compared with B/H/O group, B/O group, OVA group and NS group, that in B/H group was also increased (P<0.05). Compared with OVA group, the level of IL-17A in the lung tissues of B/H/O group and B/O group was decreased (P<0.05), and compared with B/O group, that in B/H/O group was further decreased (P<0.05). CONCLUSION: Combined vaccination of BCG and HepB reduces the inflammotory responses in the lung tissues of asthmatic mice. The mechanism may be related with the decrease in the release of IL-4, the increase in IFN-γ/IL-4, and the inhibition of IL-17A expression.     

Effects of CpG-oligodeoxynucleotides and dexamethasone on airway remodeling and expression of MMP-9 and TIMP-1 in murine model of chronic asthma

AIM: To observe the changes of airway inflammation and remodeling in a murine model of chronic asthma with CpG- oligodeoxynucleotides(CpG ODN) and dexamethasone (DXM) treatments.METHODS: BALB/c mice were sensitized and repeatedly challenged with ovalbumin.Pathological slides were prepared from left lung and stained with hematoxylin-eosin.WAmus (smooth muscle area),Wamuc (mucous area) and WAi (inner wall area) of the airway were measured and standardized by Pbm (basement membrane perimeter). The areas of collagen Ⅰand Ⅲ in the lung tissue were determined by using a Sirius red-polarizing microscopy morphometry method.Expressions of matrix metalloprotease-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by immunohistochemistry.RESULTS: WAmus/Pbm,WAmuc/Pbm and WAi/Pbm decreased significantly in CpG ODN and DXM treated group when compared with asthma group (P<0.05).No statistical significance between CpG ODN and DXM treated group was observed (P>0.05).Collagen deposition in asthma group increased more than that in CpG ODN and DXM treated group (P<0.05).The expressions of MMP-9 and TIMP-1 were much higher in asthma group than those in CpG ODN and DXM treated group (P<0.05).It had no statistical significance between CpG ODN and DXM treated group (P>0.05).CONCLUSION: Airway remodeling occurrs in the chronic asthma.Early intervention with steroid or CpG might partially inhibit its process via lowering expressions of MMP-9 and TIMP-1 in chronic asthma.     

Cucurbitin E relieves airway inflammation by inhibiting MAPKs/NF-κB signaling pathways in asthmatic mice

AIMTo investigate the effects of cucurbitacin E on airway inflammation and the signaling pathways of MAPKs and NF-κB in asthmatic mice. METHODSHealthy mice (n=40) were randomly divided into control group, model group, low-dose cucurbitacin E group, high-dose cucurbitacin E group and dexamethasone group. Ovalbumin sensitization was used to induce asthma in the mice. The protein levels of p-JNK, p-ERK1/2, p-p38 MAPK and p-p65 in the lung tissues were determined by Western blot. RESULTSCompared with control group, the numbers of inflammatory cells, such as eosinophils, lymphocytes and neutrophils, were significantly increased in model group, and the activity of MAPKs and NF-κB signaling pathway-related proteins was significantly enhanced. Cucurbitin E at high dose attenuated airway inflammation in asthmatic mice, and significantly inhibited the activity of MAPKs and NF-κB signaling pathway-related proteins. Histopathological results showed proliferation of goblet cells and bronchial mucosal epithelial cells, infiltration of inflammatory cells in the alveoli, and narrow alveolar cavity in model group, while the pathological changes were significantly alleviated in cucurbitin E treatment groups. CONCLUSION Cucurbitin E improves airway inflammation in asthmatic mice, and its mechanism may be related to the inhibition of MAPKs and NF-κB signaling pathways.     

Effects of Maxing-Shigan decoction on airway remodeling and expression of MMP-9 and TIMP-1 in lung tissues of asthmatic mice

AIM:To investigate the effects of Maxing-Shigan decoction on airway remodeling and expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the lung tissues of asthmatic mice, and to explore its possible mechanism in treatment of asthma. METHODS:The BALB/c mice were divided into blank control group, model group, low-dose Maxing-Shigan decoction group, middle-dose Maxing-Shigan decoction group, high-dose Maxing-Shigan decoction group and positive control group. The mice were sensitized and challenged with ovalbumin to establish asthma model. The mice in blank control group and model group were given saline by oral administration before 30 min of suscitation. The mice in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups were given Maxing-Shigan decoction at 5.0 g/kg, 10.0 g/kg and 20.0 g/kg, respectively, by oral administration before 30 min of suscitation. The mice in positive control group was given dexamethasone at 0.005 g/kg by oral administration before 30 min of suscitation. After consecutive administration for 7 d, the variations of airway responsiveness, the percentage of the goblet cells, the collagen deposition, and the eosinophil (EOS) counts in bronchoalveolar lavage fluid (BALF) of each group were observed. The protein levels of MMP-9 and TIMP-1 in the lung tissues were determined by ELISA and Western blot. The mRNA expression of MMP-9 and TIMP-1 was detected by RT-qPCR. RESULTS:Compared with blank control group, the airway responsiveness, the goblet cell percentage, the collagen deposition, the EOS counts in BALF, the protein levels of MMP-9 and TIMP-1, and the mRNA expression of MMP-9 and TIMP-1 were significantly increased in model group (P<0.01). Compared with model group, all of the indexes were reversed in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups and positive control group (P<0.05 or P<0.01). CONCLUSION:Maxing-Shigan decoction improves airway remodeling in asthma model mice by down-regulating the expression of MMP-9 and TIMP-1.     

Effects of PFOA exposure on inflammatory mediators IL-4, IFN-γ and glucocorticoid receptor in asthmatic mice

AIM: To investigate the effects of perfluorooctanoic acid (PFOA) exposure on the changes of asthmatic mouse airway inflammation, inflammatory mediators interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum, and glucocorticoid receptor (GR) expression in the lung tissue.METHODS: BALB/c mice (n=30) were randomly divided into 5 groups:normal control (C) group, asthma (A) group, asthma+low-dose PFOA (AP10) group, asthma+ mode-rate-dose PFOA (AP50) group and asthma+high-dose PFOA (AP100) group. Asthma model and PFOA exposure model of mice were established according to the grouping. The animals were sacrificed and their lungs were collected for HE staining, transmission electron microscopy, Western blot and immunohistochemical staining. ELISA was applied to detect the levels of IL-4 and IFN-γ in the serum.RESULTS: HE staining of the lungs showed that the asthmatic mice, compared with the normal control mice, had obvious mucus secretion around the airways and infiltration of inflammatory cells around airways and blood vessels, and the effects were much more marked in AP groups. Ultrastructural alteration of the lung tissues in the asthmatic mice were indicated by transmission electron microscopy. Compared with C group, the results of ELISA in A group and AP groups proved that IL-4 in the serum was increased and IFN-γ was decreased significantly (P<0.05). Compare with A group, IL-4 was significantly increased and IFN-γ was decreased in AP100 group (P<0.05), and no difference of those between AP10 group and AP50 group was found. The results of Western blot indicated that GR protein expression in the asthmatic mice were decreased compare with the normal mice (P<0.05), and no difference of that among A group and AP groups was observed. Immunohistochemical staining manifested that GR protein was mainly located in the cytoplasm of bronchial columnar epithelial cells, airway smooth muscle cells and vascular smooth muscle cells.CONCLUSION: Acute airway PFOA exposure in asthmatic mice dose-dependently exacebates lung inflammation by inducing Th2 type immune responses, promotes infiltration of inflammatory cells and mucus secretion around the airways and blood vessels, and destroys the ultrastructure of the lung tissues.     

Effect of BCG on experimental asthma in a guinea pigmodel of allergen sensitization

AIM: To examine the effect of bacillus calmette-guerin (BCG) on experimental asthma in guinea pigs. METHODS: Guinea pigs were sensitized with BCG and then with ovalbumin (ip). Two weeks later, guinea pigs were challenged with ovalbumin (OVA) aerosol inhalation. Thirty one Guinea pigs were divided into three groups at random control group,OVA-treated group, BCG and OVA-treated group.RESULTS: Ovalbumin inhalation caused a marked airway infiltration of eosinophils and all the animals exhibit asthmatic symptoms. Pretreatment with BCG induced typical increase in lymphocytes and monocytes in peripheral blood and in bronchoalveolar lavage fluid (BALF). BCG markedly inhibited eosinophil infiltration and attenuated the asthmatic symptoms. CONCLUSION: These data suggest that BCG exerts an inhibitory effect on asthmatic inflammation.     

Chronic exposure to house dust mite induces airway remodeling related to Th1 inflammation in mice

AIM: To investigate the inflammatory characteristics in the airway of mice with chronic exposure to dust mite. METHODS: The α-SMA-Cre/R26R transgenic reporter mice were intranasally exposed to dust mite extract for 60 d (DME group), and then subjected to the measurement of lung resistance. The performance of bronchoalveolar lavage, pathological changes of the lung tissues and splenocytes isolation 24 h after the last challenge were observed. The protein extracts from the lungs were subjected to the detection of α-smooth muscle actin (α-SMA) by Western blotting. The supernatants of the lung homogenate were collected for testing the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) with enzyme-linked immunosorbent assay. CD4⁺ T-cell subsets of the splenocytes were analyzed by flow cytometry.RESULTS: The mice chronically exposed to dust mite extract demonstrated severe airway hyperresponsiveness. The pulmonary pathological sections with HE staining manifested strong evidence of airway remodeling in DME group, corresponding to an enhanced X-gal staining that is related to α-SMA activation in the subepithelial basement membrane of bronchia. Total cell and lymphocyte counts were increased in the lungs of DME group compared to control group. No difference was found in eosinophil count of mice between DME and control groups. There was an elevated level of IFN-γ in the lungs of DME challenged mice coordinated with an increased proportion of IFN-γ-producing CD4⁺ T cells in the splenocytes.CONCLUSION: Chronic exposure to dust mite in the mice induces Th1-dominant inflammation with an airway hyperresponsiveness and the development of airway remodeling.     

Histamine receptor antagonist prevent and ameliorate airway remodeling and acid-base imbalance in asthma of guinea pig

AIM:To investigate the effect of histamine receptor antagonist on airway remodeling and acid-base imbalance in asthma of guinea pig. METHODS:Guinea pigs were divided into 5 groups: the normal control group, the asthma model group, the continued asthma model group, histamine group and histamine receptor antagonist group. For each group, the content of histamine, Na+, Cl-, PaO2, PaCO2, pH, AB, SB in serum, and thickness of airway mucosa and smooth muscle cell layer were measured and compared with each other. RESULTS:(1) According to the content of histamine in serum and thickness of airway mucosa and smooth muscle, the order was: the histamine group>continued asthma model group>the asthma model group>the normal control group (P<0.01), and the histamine receptor antagonist groupthe continued asthma model group (P<0.01), but for PaCO2, the order was conversed. Airway remodeling, increase in histamine in serum, respiratory acidosis and metabolic acidosis in asthmatic guinea pig were observed. Exogenous histamine accentuated the change, however, histamine receptor antagonist attenuated it. CONCLUSION:Histamine may take part in the airway remodeling of asthma. Histamine receptor antagonist can prevent and ameliorate airway remodeling and acid-base imbalance in asthma of guinea pig.     

Influence of Jiaomu oil A2 on eosinophil manifold and CD34+ with marrow granule system mobilization in bronchia asthma mice

AIM: To observe the influence of Jiaomu oil A2 on eosinophil manifold and CD34+ with marrow granule system mobilization in bronchial asthma mice. METHODS: The asthmatic mouse model was established by sensitization and challenge of the animals with 20% Al(OH)3+10% ovalbumen (OVA). After the mice were excitated for 10 d and giving medical therapy at the same time, the mice were executed, the bronchial-alveolar lavage inflammatory cells and the hemocytopoiesis cells were examined using Wrish-Giemsa staining. The expressions of interleukin-5 (IL-5) and eotaxin (EON) in lung tissue and marrow were examined by in situ hybridization. The expression of IL-5 and EON albumen in lung tissue and marrow were detected by immunohistochemistry. The inflammatory cell infiltration and CD34+ cells in lung tissue were also observed by HE and immunofluorescence staining. RESULTS: Both Jiaomu oil A2 and prednisone significantly attenuated the pathological process degree of bronchial inflammatory reaction such as tissue swelling, reconstruction, hyperplasia, and epithelial cell shedding, and inhibited eosinophil count and infiltration caused by stimulation of allergic effect. Moreover, the two drugs markedly lessen the eosinophil density in tracheal surrounding tissue and marrow in asthma mice and depressed the differentiation of marrow myelocyte to eosinophil. Finally, the apparent decrement of CD34+IL-5, CD34+IL-5R, CD34+CCR-3 cells in bronchial tissue and marrow showed some relationship with the downregulation of IL-5, IL-4, GM-CSF in lung tissue. CONCLUSION: The effect of Jiaomu oil on airway inflammation in asthma mice is associated with inhibiting the mobilization of eosinophil and marrow granule system.     

Effect of intranasal treatment with Toll-like receptor 9 ligand CpG oligodeoxynucleotides on airway inflammation in mice with allergic combined airway disease

AIM: To investigate the therapeutic effect of intranasal administration of CpG oligodeoxynucleotides (CpG-ODN), compared with intradermal administration, on lower airway inflammation in ovalbumin (OVA)-induced allergic combined airway disease (ACAD) mouse model.METHODS: Totally 30 female BALB/c mice aged from 6 to 8 weeks were randomly divided into control group, allergic rhinitis model group (AR group), ACAD group, ACAD intranasally treated with CpG-ODN group (CpG i.n. group) and ACAD intradermally treated with CpG-ODN group (CpG i.d. group). The mice were sensitized and challenged with OVA. Treatment with CpG-ODN was also performed during challenge, either intranasally or intradermally. Immunologic variables and nasal symptom were studied.RESULTS: Compared with CpG i.d. group and ACAD group, the percentage of eosinophils from bronchoalveolar lavage fluid (BALF), the levels of Th2 cytokine production in BALF and supernatants of cultured splenic lymphocytes, OVA-specific IgE from blood, peribronchial inflammation score in the lung, and nasal symptoms were significantly reduced in CpG i.n. group.CONCLUSION: Allergic rhinitis treated by CpG-ODN has a significant improvement on lower airway inflammation in ACAD mouse model; and it may be more effective when administrated intranasally than intradermally.     

Role of connective tissue growth factor in airway remodeled in rats induced by repeated bacterial infection

AIM: To investigate the role of connective tissue growth factor (CTGF) in airway remodeling in rats induced by repeating Pseudomonas aeruginosa (PA) infection. METHODS: The rats were intratracheally injected with PA for 12 times to induce chronic lung inflammation. The pathological changes of the trachea and lungs were observed, and the thickness of the trachea wall and vessel wall was measured. At the same time, the methods of immunochemistry and real-time quantitative RT-PCR were used to determine the protein and mRNA expression of CTGF in the lung tissues. The relevance between pathological changes and CTGF expression was also analyzed. RESULTS: From the 4th week, the thickness of the trachea wall and vessel wall in infectious group was larger than that in NS group (P<0.05). At the 16th week, obvious chronic inflammation in all grade bronchi appeared, the trachea walls were thickened and the lumens were narrowed in the infected animals. The expression of CTGF was significantly up-regulated (P<0.01) with positive correlations to the thickness of the trachea wall and vessel wall (r=0.880, r=0.829,P<0.01). CONCLUSION: Airway remodeling in rats is induced by repeated injection of PA. CTGF may play some roles in the pathogenesis of airway remodeling.     

Effect of hydrogen sulfide on airway inflammation induced by ozone in mice

AIM: To investigate the effect of hydrogen sulfide (H₂S) on airway inflammation induced by ozone (O₃) exposure and its mechanisms.METHODS: C57BL/6 mice (n=32) were randomly divided into control group, O₃ group, NaHS+O₃ group and NaHS group. The mice in O₃ group and O₃+NaHS group were exposed to 2.14 mg/m³ O₃ for 3 h on days 1, 3 and 5, while the mice in control group and NaHS group were exposed to filtered air. NaHS (14 μmol/kg) was administered intraperitoneally to the mice in NaHS group and O₃+NaHS group 30 min before each exposure. After the last exposure for 24 h, the airway responsiveness was determined, and bronchoalveolar lavage fluid (BALF) was collected for counting inflammatory cells and measuring total protein concentration. The lung tissues were collected for observing the morphological changes with HE staining. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), malondialdehyde (MDA) and NF-κB p65 protein in the lungs were determined.RESULTS: Compared with control group, the airway responsiveness, inflammatory cells, protein concentration, inflammation score, levels of IL-6, IL-8, MDA and NF-κB p65 in O₃ group increased significantly, but these in NaHS+O₃ group decreased compared with O₃  group.CONCLUSION: The present findings suggest that H₂S attenuates O₃ induced airway inflammation by inhibiting NF-κB expression and preventing lipid peroxidation.     

Effect of Kechuanning on airway remodeling and protein level of p-ERK1/2 in lung tissues of asthmatic rats induced by virus

AIM:To investigate the effect of Kechuanning on airway remodeling and the protein level of p-ERK1/2 in lung tissues of asthmatic rats induced by virus. METHODS:The asthmatic rat model induced by respiratory syncytial virus was established. The experimental rats were divided into normal group, asthma model group, low dose (0.33 mL/kg), middle dose (3.0 mL/kg) and high dose (10 mL/kg) of Kechuanning groups, and PD98059 (3 mg/kg) group. The airway responsiveness of the rats was measured by animal ventilator. The pathological changes of the lung tissues were observed by HE staining. PAS staining and Masson staining were used to observe goblet epithelial cells metaplasia and airway collagen deposition. The expression of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the lung tissues of the rats was detected by immunohistochemical staining. The protein levels of ERK1/2 and p-ERK1/2 were determined by Western blot. RESULTS:Compared with model group, the airway responsiveness of the rats in middle dose and high dose of Kechuanning groups was significantly decreased (P<0.01), the injury of lung tissues was significantly decreased, the goblet epithelial cells metaplasia and airway collagen deposition were significantly reduced (P<0.01), and the expression of MMP-9 and TIMP-1 in the lung tissues was also significantly decreased (P<0.01). In addition, the protein level of p-ERK1/2 in high dose of Kechuanning group was significantly decreased compared with model group (P<0.01). CONCLUSION:Kechuanning may treat asthma by regulating the expression of p-ERK1/2 in the lung tissues and improving the airway remodeling symptoms of asthmatic rats induced by virus.