OBJECTIVETo observe the effect of Wenyang Yiqi Pingchuan Recipe (WYPR) on the pathomorphology of lung and its regulation on lung tissue contents of nitric oxide (NO) and endothelin-1 (ET-1) in rats with bronchial asthma.

METHODSSixty SD rats were randomly divided into 6 groups: the normal group, the model group, and the four treated groups treated with high dose WYPR, low dose WYPR, Guilong Kechuanning Capsule and aminophylline, respectively, 10 in each group. Except those in the normal group, all rats of bronchial asthma model were established by egg protein sensitization and provocated by inhalation. The treatments were given via gastrogavage every day starting from the first provocation (the 3rd week of modeling) to the execution. Rats were sacrificed after 4-week treatment, their lung was taken for determining the contents of NO and ET-1, and histopathological changes in lung were observed as well.

RESULTSCompared with the normal group, the contents of NO and ET-1 in the lung tissue, the thickness of bronchus wall and bronchus smooth muscle, the number of eosinophil granulocytes increased in the model group and the low dose WYPR group, showing statistical significance (P < 0. 01). As compared with the model group, all the above-mentioned indices were lower in all the 4 treated groups (P < 0.05 or P < 0.01), but the lowering in the WYPR treated groups (either high or low dose) was more significant than in the Guilong Kechuanning treated group (P < 0.05 or P < 0.01); while compared with the aminophylline treated group, the high dose WYPR group was superior in reducing eosinophile granulocytes (P < 0.01), but no significance between them was shown in NO and ET-1 levels (P > 0.05).

CONCLUSIONSWYPR could reduce the eosinophilic infiltration, decrease the contents of NO and ET-1 in the lung tissue, restrain the air passage inflammation and inhibit the pathological process as airway remodeling.

Animals ; Asthma ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; metabolism ; Inflammation ; pathology ; Lung ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThymic stromal lymphopoietin (TSLP) plays an important role in initiating dendritic cell mediated allergic inflammation. This study was designed to examine the effects of inhaled budesonide on TSLP expression in the lung tissues and on the bronchial-pulmonary pathology in asthmatic rats.

METHODSThirty-two female Sprague-Dawley rats were sensitized and challenged with inhaled ovalbumin (OVA) to induce asthma. The asthmatic rats were randomly divided into 2 groups on the 22nd day of OVA challenge: a budesonide treatment group that received inhaled budesonide at 0.32 mg/kg daily for 7 days and an asthma control group that received inhaled 0.9% normal saline for 7 days. TSLP expression in the lung tissues was measured by Western blot and fluorescent-immunohistochemistry 29 and 36 days after OVA challenge. Bronchial-pulmonary pathological changes were evaluated by hematoxylin & eosin and periodic acid-schiff staining.

RESULTSBudesonide treatment alleviated airway inflammation when compared with the asthma control group 29 days after OVA challenge. However, the airway inflammatory reactions were aggravated in the budesonide treatment group 36 days after OVA challenge (7 days after budesonide discontinuance). TSLP expression in the lung tissues was significantly lower in the budesonide treatment group than that in the asthma control group both 29 and 36 days after OVA challenge (P<0.05).

CONCLUSIONSInhaled budesonide can inhibit the TSLP expression in the lung tissues and alleviate lung inflammatory reactions in asthmatic rats, but there is end-of-dose failure.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Blotting, Western ; Bronchi ; pathology ; Budesonide ; administration & dosage ; Cytokines ; analysis ; Female ; Immunohistochemistry ; Lung ; pathology ; Rats ; Rats, Sprague-Dawley

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.
Acetylcysteine/*analogs & derivatives/therapeutic use ; Animals ; Asthma/drug therapy/*immunology/pathology ; Bronchial Hyperreactivity/*drug therapy/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Mice ; NF-kappa B/*metabolism ; Ovalbumin/immunology ; Reactive Oxygen Species/*metabolism ; Vascular Endothelial Growth Factor A/metabolism

OBJECTIVETo explore the role of transient receptor potential canonical 1 (TRPC1) in airway remodeling and the effect of budesonide intervention on its expression in the lungs of guinea pigs with ovalbumin-induced asthma.

METHODSFifty male guinea pigs were randomized into 5 equal groups, including a blank control group, ovalbumin group, ovalbumin+TRPC1 siRNA group, ovalbumin+luciferase siRNA group, and ovalbumin+budesonide group. After corresponding treatments, bronchoalveolar lavage was collected from the guinea pigs for eosinophils analysis and detection of IL-5 and IL-13 levels using ELISA. The lung tissues were stained with HE and Masson's trichrome to observe the bronchial wall thickness, smooth muscle hypertrophy, subepithelial collagen deposition, and lung inflammations. Immunohistochemistry and real-time quantitative PCR were performed to detect TRPC1 protein and mRNA expressions in the lungs, respectively.

RESULTSThe guinea pig models of ovalbumin-induced asthma showed significantly increased thickness of the bronchial wall, smooth muscle hypertrophy, collagen deposition and inflammatory cell infiltration, but these pathologies were obviously alleviated by treatment with TRPC1 siRNA or budesonide (P/0.05). Immunohistochemstry showed that TRPC1 protein was distributed mainly on the cell membrane and in the nuclei of the basal cells or columnar epithelial cells.

CONCLUSIONThe up-regulated expression of TRPC1 ion channel is closely associated with the occurrence and progression of airway remodeling and chronic airway inflammation in asthma. Budesonide can partially suppress airway remodeling and inflammation by regulating the expression of TRPC1.

Airway Remodeling ; Animals ; Asthma ; drug therapy ; metabolism ; Bronchi ; pathology ; Budesonide ; pharmacology ; Disease Models, Animal ; Guinea Pigs ; Inflammation ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-5 ; metabolism ; Leukocyte Count ; Lung ; drug effects ; metabolism ; Male ; Ovalbumin ; TRPC Cation Channels ; metabolism

OBJECTIVETo study the expression of stromal cell derived factor-1(SDF-1) and CXC chemokine receptor 4 (CXCR4) in the airway and the effect of budesonide on their expression in mice with asthma.

METHODSThirty BALB/c male mices were randomly divided into three groups: placebo control, untreated asthma, and budesonide-treated asthma. The asthma group were induced by intraperitoneal injection of 10% ovalbumin (OVA ) on days 1, 8 and 15, and then from days 22 to 34, challenged by inhalation of 2% OVA aerosol every other day. The budesonide-treated asthma group received an inhalation of budesonide (1 mg ) before OVA challenge. The pathological changes of the airway were assessed by hematoxylin and eosin staining. The immunohistochemistry was used to estimate the expression of SDF-1 in the lung. RT-PCR was used to evaluate the expression of CXCR4 in the lung.

RESULTSCompared with the control group, SDF-1 and CXCR4 expression in the lung in the untreated asthma group increased significantly (p<0.05). The budesonide-treated asthma group demonstrated significantly decreased SDF-1 (0.426+/-0.052 vs 0.361+/-0.065; p<0.05) and CXCR4 (0.829+/-0.027 vs 0.723+/-0.094; p<0.05) expression in the lung as compared with the untreated asthma group. Both SDF-1 (r=0.744, p<0.01) and CXCR4 (r=0.553, p<0.01)were positively correlated with the thickness of the airway wall.

CONCLUSIONSSDF-1 and CXCR4 may be associated with airway remodeling in mice with asthma. Budesonide can improve airway remodeling, possibly by decreasing the expression of SDF-1 and CXCR4.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Budesonide ; pharmacology ; Chemokine CXCL12 ; analysis ; Male ; Mice ; Mice, Inbred BALB C ; Receptors, CXCR4 ; analysis ; genetics

Animals ; Asthma ; drug therapy ; metabolism ; Inflammation ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Phytotherapy ; Pyrazines ; pharmacology ; therapeutic use ; RNA, Messenger ; metabolism ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism

OBJECTIVETo investigate the effects of ligustrazine (LTZ) on airway inflammation in a mouse model of neutrophilic asthma (NA).

METHODSForty healthy C57BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone (DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ (80 mg/kg) or DXM (0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid (BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin (IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining.

RESULTSThe airway responsiveness of the NA group was signifificantly higher than the normal control group (P<0.05), while those in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05), and those in the LTZ group were signifificantly lower than the DXM group (P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in fifiltration in the NA group. The airway inflflammation in the LTZ and DXM groups were signifificantly alleviated than the NA group. The infifiltration in the LTZ group was signifificantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was signifificantly increased and the IL-10 level in BALF was signifificantly decreased in the NA group (P<0.05). LTZ and DXM treatment signifificantly decreased IL-17 levels and increased IL-10 levels compared with the NA group (P<0.05), and the changes in the above indices were more signifificant in the LTZ group (P<0.05).

CONCLUSIONLTZ could alleviate the airway inflflammation in the NA mice model through increasing the IL-10 level and decreasing the IL-17 level.

Animals ; Asthma ; blood ; complications ; drug therapy ; pathology ; Bronchoalveolar Lavage Fluid ; cytology ; Disease Models, Animal ; Female ; Interleukin-10 ; metabolism ; Interleukin-17 ; metabolism ; Leukocyte Count ; Lung ; drug effects ; pathology ; Mice, Inbred C57BL ; Neutrophils ; drug effects ; pathology ; Pneumonia ; blood ; complications ; drug therapy ; pathology ; Pyrazines ; pharmacology ; therapeutic use ; Respiratory Hypersensitivity ; blood ; complications ; drug therapy ; pathology

OBJECTIVETo study the effects of 1,25-(OH)(2)D(3) on airway remodeling and expression of high mobility group box 1 (HMGB1) and IL-17 in asthmatic mice.

METHODSFifty female mice were randomly divided into 5 groups: control, asthma, low-dose, middle-dose, and high-dose intervention groups (n=10 each). Asthma was induced by intraperitoneal injections of ovalbumin (OVA) and aerosol inhalation of OVA solution. The low-dose, middle-dose, and high-dose intervention groups were administered with 1,25-(OH)(2)D(3) solution at the dosage of 1, 4 and 10 μg/kg respectively by intraperitoneal injections before asthma challenge. The airway structural changes were assessed by hematoxylin and eosin staining. mRNA expression levels of HMGB1 and IL-17 in the lung tissues were evaluated by RT-PCR. The protein levels of HMGB1 and IL-17 in the lung tissues were observed by immunohistochemistry.

RESULTSThe airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were higher in the untreated asthma group than in the control group (P<0.05). The airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were lower in the middle-dose and low-dose intervention groups than in the untreated asthma group, and the middle-dose intervention group demonstrated lower airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 than in the low-dose intervention group (P<0.05). However, the airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 in the high-dose intervention group were higher than in the untreated asthma group (P<0.05).

CONCLUSIONSHMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of HMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of 1,25-(OH)(2)D(3) can improve the airway remodeling, but a higher dose of 1,25-(OH)(2)D(3) may affect adversely the airway remodeling process.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Calcitriol ; pharmacology ; Dose-Response Relationship, Drug ; Female ; HMGB1 Protein ; analysis ; genetics ; physiology ; Interleukin-17 ; analysis ; genetics ; physiology ; Lung ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo investigate whether erythromycin exerts anti-inflammatory effect on allergic airway inflammation and whether erythromycin modulate allergic airway inflammation by inhibiting nuclear factor kappa B (NF-kappa B) activation.

METHODSOvalbumin (OVA) together with aluminum hydroxide and Bordetella Pertussis was injected intraperitoneally to immunize SD rats and two weeks later 1% OVA was inhaled to challenge them for consecutive 7 days to mimic allergic airway inflammation. In treatment group, erythromycin was given orally (180 mg/kg.d) during the course of allergen exposure. WBC counts in bronchoalveolar lavage fluid (BALF) and lung specimen analysis were used to describe lung tissue inflammation. The expression of NF-kappa B subunit p65 in cell nucleus of lung tissue was measured by immunohistochemistry and NF-kappa B binding activation in lung tissue by electrophoresis mobility shift assay (EMSA).

RESULTSLung tissue specimen analysis indicated that the severity of allergic inflammation was reduced in treatment group. The number of total WBC in BALF (x 10(8)/L) (31 +/- 22) was lower than that in model group animals (66 +/- 28), P < 0.01. The number (x 10(3)/mm(2)) of cells with nuclear staining of NF-kappa B per square millimeter of submucosal region around large bronchus (1.4 +/- 0.4) was lower than that in model group animals (2.6 +/- 0.6), P < 0.01. NF-kappa B binding activity (32 +/- 14) was lower than that of model group (46 +/- 17), P < 0.05.

CONCLUSIONErythromycin had an obvious protective role in allergic airway inflammation. Erythromycin inhibited NF-kappa B transcriptional activity to exert anti-inflammatory effect.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Asthma ; drug therapy ; Erythromycin ; pharmacology ; Lung ; pathology ; Male ; NF-kappa B ; analysis ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.

METHODSForty male SD rats were randomly divided into four groups: Group A (normal control), Group B (asthma group), Group C (CRTH2 antagonist BAYu3405 treatment group), Group D (DP1 antagonist BWA868C treatment group). Asthma was induced by ovalbumin (OVA) challenge. The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils (EOS) were measured by radiological binding assay (RBA). The left lungs were used for histological examinations and bronchoalveolar lavage fluid (BALF) was collected from the right lungs. The total cell numbers, EOS absolute count and differential cell counts in BALF were performed. Serum concentrations of IL-4, 5 and IFN-gamma were measured by ELISA.

RESULTSRats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group. Serum concentrations of IFN-gamma in rats of BAYu3405 treatment group increased, but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group (P<0.01), and BALF EOS count was decreased significantly (P<0.01). Peripheral blood EOS count was higher than that in rats of normal control group, but was not significantly different from that in rats of asthma group and BWA868C treatment group. The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group, BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A (P<0.01). There was no significant difference in DP1 among all the groups (P>0.05).

CONCLUSIONCRTH2, but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; pathology ; Bronchi ; immunology ; pathology ; Carbazoles ; pharmacology ; therapeutic use ; Inflammation ; drug therapy ; Male ; Ovalbumin ; Prostaglandin D2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; antagonists & inhibitors ; Receptors, Prostaglandin ; antagonists & inhibitors ; Sulfonamides ; pharmacology ; therapeutic use