The Influence Of Heme Oxygenase-1 And Fudosteine On The Expression Of MUC5AC And IL-25 In Asthma Mice

Objective:To observe the effects of heme oxygenase-1 and fudosteine on the expression of MUC5AC and IL-25 in asthmatic mice.To analyse the role of heme oxygenase-1,MUC5AC,IL-25 in the pathogenesis of asthma,to explore the mechanism of heme oxygenase-1 in bronchial asthma pathogenesis,then to provide a new approach to asthma airway mucus hypersecretion therapy.Methods:28 Balb/c mice were randomly devided into four group:asthma group(A),heme oxygenase-1 intervention group(H),fudosteine interv-ention group(F),blank control group(B).The asthma group:mice were immunized in the first day and the 14th day by intraperitoneal injection of freshly prepared chicken ovalbumin OVA 100ug,aluminum hydroxide 100ug and saline 0.2ml.The 25th day began to stir,the mice were placed in a transparent container,with 2.5%OVA 40ml atomization inhalation,30 minutes,once a day,for 3 consecutive days.Heme oxygenase-1 group:each mice was sensitized as asthma group,and intraperitoneal injection of hemin 75 μmol/kg in 2nd day、1st day before sensitization,and 12th day,13th day,14th day,23th day,24th day,27th day after sensitization.Fudosteine intervention group:each mice was sensitized as asthma group,and took fudosteine 200mg/kg by gastric gavage on 25th day,26th day,27th day,30min before stimulation.Blank control group:each mice was intraperitoneal injection and inspired with 0.2ml saline.All mice were killed after the last stimulation in 24 hours,ocular blood and lung tissue were taken.Assess the lung tissue and the inflammatory by HE staining,detect the expression of MUC5AC、HO-1 in lung tissue by imunohistochemistry;measure the content of IL-25 in serum,MUC5AC in lung tissue by enzyme-linked immunosorbent assay(ELISA).All date was expressed with by using statistical data processing software system SPSS 17.0,One way analysis of variance was applied in different groups,and p<0.05 was significant difference.Results:(1)Pulmonary histopathological HE staining:A group has edema in mucosa,many inflammatory cells were infiltrated in small airways and small blood vessels,and eosinophils,monocytes,red blood cells,alveolar septal fracture was appeared in alveolar space.B group,the lung tissue of mice trachea mucosa without the pathologic changes.H group,the alveoli and alveolar interstitial with less inflammatory cells and exudation,visible absorption of inflammation.F group,the lung tissue of mice with a small amount of inflammatory cell infiltration,less exudation and inflammation absorption.(2)Immunohistochemistry:1)The expression of MUC5AC in lung tissue:B group:MUC5AC negative expression,tracheal epithelium without stained yellow.A group:MUC5AC expression was strongly positive,mainly in the bronchi,bronchiole epithelial cells,airway basal layer,alveolar septum,perivascular expression,mainly for the yellow,brown yellow or brown.F group and H group:MUC5AC was weakly positive expression.2)The expression of HO-1 in lung tissue:B group:the expression of HO-1 was negative,tracheal epithelial cells without yellow.A group:HO-1 expression was strongly positive,mainly in bronchial,bronchiolar epithelial cells and airway basal,a small amount of expression in lung interval,mainly for the yellow,brown yellow or brown.F group:the expression of HO-1 was positive,but less than the asthma group,hemin group.H group:HO-1 expression was strongly positive,in airway epithelial cells,pulmonary septal.(3)The expression of IL-25 in serum and MUC5AC in lung tissue:IL-25 content:asthma group was the highest,followed by fudosteine group,hemin group,the control group was the lowest;the MUC5AC content:asthma group was the highest,followed by hemin group,fudosteine group,the control group was the lowest.The difference between each group was statistically significant(P<0.05).Conclusions:1、Balb/c mouse asthma model was established successfully.2.Asthma mice which was sensitized and inspired by OVA had airway mucus hypersecretion,increased the expression of HO-1 in lung tissue.3、Asthma mice which was sensitized and inspired by OVA,the expression of MUC5AC and IL-25 increased.There was a positive correlation between them.4、Heme oxygenase-1 and fudosteine down-regulate of MUC5AC and IL-25 expression.But the effects of them are different,to inhibit the expression of MUC5AC,fudosteine is better than heme oxygenase,1;in the regulation of IL-25 and reduce the airway inflammation of asthma,heme oxygenase-1 is better than fudosteine.