| Objectives: Bronchial asthma(the astnma) is a major chronic respiratory inflammatory disease,which severely threatens the worldwide public health. About 150 million people worldwide suffer from asthma.The prevalence of children asthma is about 1%.In some places it is more than 3%,and it has a clear upward trend year by year.It is a major disease affecting factors in decli- ning the quality of life of children.Asthma is a chronic airway inflammatory disease with a number of inflammatory cells such as eosinophils(EOS),mast cells and lymphocytic infiltration which caused by allergens or other factors in a state of bronchial hyperresponsiveness.A large number of inflammatory cells and inflammatory mediators in the airway can lead to the changes of airway wall cells and composition followed by remodeling occurred.Gucocorticoid is the most effective anti-inflammatory drugs in asthma prevention and treatment, but just inhalation will also have adverse effects on the human body. Aminop- hylline is one of main drugs in asthma treatment.A new study shows that ami- nophylline can not only expand the bronchial smooth muscle,but also have anti-inflammatory effects.But its mechanism has not yet understood clearly.In my study,we observes the treatment effects of aminophylline on airway infla- memation and airway remodeling in asthmatic rats by measuring interleukin- 25(IL-25), interleukin-12(IL-12),nuclear transcription factor-κB(NF-κB) and matrix metalloproteinase-9 (MMP-9) changes to explore the mechanisms of aminophylline in asthma treatment.Methord: 30 Wistar male rats in ages of 8 to 12 weeks and body weight (160±20)g were randomly divided into normal control group(10),asthmatic model group(10) and aminophylline treatment group(10).Each rat in asthmatic model group and aminophylline treatment group was sensitized by intraper- itoneal injection with 1ml saline including 100mg ovalbumin (OVA) and 100mg aluminum hydroxide on 1st day,8th day and the 15th day,while the normal control group was sensitized by the same amount of saline.On the 22nd day the rats of asthmatic model group were placed in a not completely closed home-made plexiglass box.The 1% OVA solution was sprayed by a compressed air pump to stimulate the rats 20 minutes once a day for a week. The rats of aminophylline treatment group were administered with amino- phylline by intraperitoneal injection at a dose of 60mg·kg-1 before stimulated by OVA in each time 30 minutes ago,while the rats of normal control group were stimulated by the physiological saline.In each group,the rats were anes- thetized with 10% chloralhydrate by intraperitoneal injection at a dose of 3.5 ml·kg-1 in the last 24 hours after induced asthma.The right femoral arteries were saeparated,the roots were cut and the blood samples were collected.IL-12 and IL-25 levels in serum was detected by enzyme-linked immunosorbent assay.Every rat trachea was isolated,and the left lung was ligated.In each rat the right lung was poured into 4% paraformaldehyde slowly from the trachea to tissue expansion,and then the right bronchus was ligated,the right lung was placed into the same fixative and fixed.Finally,the middle lobe of the right lung was paraffin imbedding and section, the NF-κB and MMP-9 expression were detected.Results:1 The rats'behavioral changes of asthmatic model group after stimulationThe rats of asthmatic model group shortly appeared allergies such as restless and scratching facial fur after inhaling OVA,and then proneness with immobility,breathlessness and dyspnea(obvious abdominal breathing). Sonor- ous expiratory phase stridor could be heard in some rats,following with mucus flowing from mouth and nose.Severe case appeared irregular breath. The rats'furs tarnished,low-spirited and unresponsive after iterative stimulation.2 The pathology characteristic of pulmonary tissueThe epithelial cells of the airway have normal structures, and there are not obvious inflammatory cells infiltration in mucous and below mucous in normal control group(Fig.1-1).In asthmatic model group, bronchospasm and bronchoconstriction present like chrysanthemi flos,and bronchial lumens are full of secretions.There are obvious inflammatory cells infiltration around bronchiole and small vessel,which mainly EOS,lymphocytes and neutrophils also.The alveolar septums widen,have fibrosis and are infiltrated with large of lymphocytes and macrophages(Fig.1-2).In aminophylline treatment group, there are no bronchospasm,bronchoconstriction and secretions in bronchial lumens. The inflammatory cells reduce around tubal wall and the alveolar septums pathological changes are improved(Fig.1-3).3 The effects of aminophylline on the concentrations of IL-12 and IL-25 in the serum of asthmatic ratsThe concentration of IL-12 in serum of asthmatic model group was lower than the normal control group (P <0.01) and aminophylline treatment group (P <0.01).Aminophylline treatment group was also lower than the normal control group (P <0.01,Table 1).The concentration of IL-25 in serum of asthmatic model group was higher than the normal control group (P <0.01) and aminop- hylline treatment group (P <0.01).Aminophylline treatment group was also higher than the normal control group (P <0.01,Table 1).4 The effects of aminophylline on the expression of NF-κB and MMP-9 in pulmonary tissueThe expression of NF-κB in pulmonary tissue of asthmatic model group was higher than the normal control group (P <0.01) and aminophylline treat- ment group (P <0.01).Aminophylline treatment group was also higher than the normal control group (P <0.01,Table 2).The expression of MMP-9 in pulmo- nary tissue of asthmatic model group was higher than the normal control group (P <0.01) and aminophylline treatment group (P <0.01).Aminophylline treatment group was also higher than the normal control group (P <0.01,Table 2).5 The results of correlation and regression analysis testThe concentration of IL-12 and IL-25 in serum had a significant nega- tive correlation by the testing of the pearson linear correlation and logistic regression analysis (r =- 0.767,P <0.01). The regression equation: Y=70.066- 1.237X(F=40.116,P<0.01,Fig.3).The expression of NF-κB in pulmonary tissue and the concentration of IL-12 in serum had a significant negative correlation by the same analysis (r=-0.672,P<0.01).The regression equation: Y=38.051-33.73X(F=23.018,P<0.01,Fig.4).The expression of NF-κB in pulm- onary tissue and the concentration of IL-25 in serum had a significant positive correlation(r=0.795,P<0.01).The regression equation: Y=17.249+64.371X(F= 48.238,P<0.01,Fig.5).The expression of NF-κB and MMP-9 in pulmonary tissue had a significant positive correlation (r=0.881,P<0.01). The regression equation:Y=0.093+0.521X(F=91.317,P<0.01,Fig.6).Conclusion:1 The asthmatic rats still exist subdued Th1 respond and fortified Th2 respond, which support the doctrine of imbalance of Th1/Th2 in asthma. Aminophylline can regulate the imbalance of Th1/Th2.2 Aminophylline can inhibit the expression of NF-κB in pulmonary tissue and the concentration of IL-25 in serum of asthmatic rats,thus improve inflammat- ory state.3 Aminophylline can improve airway remodeling by reducing the expression of NF-κB and MMP-9 in pulmonary tissue.4 NF-κB plays a central role in asthma,so inhibiting its pathway can improve asthmatic occurrence and development to provide a new direction for asthma treatment.
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