| Pulmonary surfactant is a mixture of lipids and proteins. Biochemical and biophysical abnormalities of PS have been reported in various lung diseases, such as acute respiratory distress syndrome, pneumonia, and cardiogenic lung edema. Today surfactant has become a fascinating compound in innate and adaptive immunity of the lung due to its immunomodulatory properties. The involvement of pulmonary surfactant in the pathophysiological process of asthma with a predominant disturbance in the conducting airways has only been addressed recently. Asthma is a kind of disease characterized by chronic inflammation of the airways with eosinophils and bronchial hyper-responsiveness, which causes reversible airway obstruction after the inhalation of various stimuli. Airway obstruction, accompanied with increased airway resistance in asthma, which is commonly thought to be caused by smooth muscle constriction, mucosal edema and secretion of fluid into the airway lumen, may partly be due to a poor function of pulmonary surfactant. In the past decade, direct and indirect evidence has emerged for surfactant as a factor in the regulation of airway calibers and a modulator of allergic inflammation. PS has several important roles in the pathogenesis of asthma. 1. SP-A, SP-D can bide and present allergen, and theyinteract closely with dendritic cell. 2. SP-A, SP-D can down-regulate activation and proliferation of lymphocytes and inhibit histamine release. 3. A feedback regulatory mechanism exists among the synthesis and secretion of surfactant, eosinophil activation and cytokine release. The composition and quantity of PS changed in asthmatic subjects, and the low function was found. In recent years, it is observed that exogenous PS has therapeutical effect to acute asthmatic attack. In asthmatic animal model, it was demonstrated that treatment with intratracheal instillation of surfactant can alleviates airway obstruction. A randomized controlled trial indicated a significant improvement in pulmonary function data after inhalation of surfactant in patients with acute asthma attacks. Now there is no report about the therapeutical effect of substitution therapy with exogenous PS to multiple pathophysiological changes such as airway remodeling. So, we attempted to explore the effect of exogenous PS to airway remodeling in asthmatic rats with image analysis method. Moreover, we studied the changes of the expression of EGF and EGFmRNA by immunohistochemistry and molecular biological methods to discuss the possible mechanism of the therapeutic effect of PS on asthmatic airway remodeling. We anticipate finding new theoretical basis for the prevention and therapy of asmatic airway remodeling.Methods: Sixty male SD rats were randomly assigned into three groups: control group (A group, 20), asthmatic group (B group, 20) and therapeutic group (C group, 20). Establish asthmatic rats model: group B and C were hypodermically injected immunogen stock suspension to be sensitized, group A was injected with the same volume isotonic Na chloride. 2 weeks after sensitization, group B and C were provocated with 1% egg albumin suspension, group A with isotonic Na chloride, ultrasonic atomizing inhalation, once quotidie, 2 weeks. Group C inhaled PS 100 mg/kg before each provocation. Observe the asthmatic attack conditions. Cytology detect inBALK After lung tissue was sectioned, we used image analysis method to measure the airway wall area, airway smooth muscle thickness and number of bronchial smooth muscle nucleus to evaluate the degree of airway remodeling. Other lung tissue was reacted with adenosine and ACH, then was sectioned. We calculated PMS with image analysis method to detected airway reactivity. The express and distribution of EGF in small airway of rats were shown with immunohistochemistry technique. The express of EGFmRNA were detected with RT-PCR.Results: (1) Asthmatic attack mainly took place in 30min after provocation, and performed as light attack. The attack of group A was 0(0/20); the rates of group B and C were 90% (18/20) and 5% (1/20) , respectively. There was highly significant difference (-*r2=28.97> PO.01) between B and C . (2) In the three indexes, total cellular score % lymphocyte count and eosinophile granulocyte count, B group increased significantly than A group. Meanwhile, C group decreased significantly than B group (PO.05). (3) Pathology observation by HE and image analysis: In group B, there were manifest bronchiospasm and massive eosinophile granulocyte infiltrations in submucosa and bronchi wall; mucus plugs could be found in Bronchial lumen. In addition, the airway wall and airway smooth muscle thickened obviously. Image analysis results indicates: in the three indexes WA/Pk SMT/Pi and N/Pi, B group increased significantly than A group. The data of C group were significantly lower than those of B, but compared with A group there wasn't any statistical significance. (4) Airway reactivity detect: (D adenosine responsiveness of airway smooth muscle to adenosine (represented by PMS) in asthmatic group was 24% higher than that in control group, but compared with asthmatic group PMS decreased 15% in therapeutic group (PO.05); (2)ACH: PMS to acetylcholine in asthmatic group increased 25% than that in control group, but compared with asthmatic group PMS decreased... |
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