Effect Of Peiyuan Asthma-reliving Decoction On Airway Remodeling In Asthmatic Mice Through IL-33/ST2L Signaling Pathway

Objective: Observe the effect of asthma-reliving decoction on IL-33/ST2 L signaling pathway and airway remodeling in asthma mice by establish-ing an asthma mouse model.Methods:Thirty two female BALB/c mice aged 6-8 weeks were random-ly divided into 4 groups,with 8 mice in each group.They were divided into blank group,model group,budesonide group,and peiyuan asthma-reliving decoction group.In addition to the blank group,the remaining 3 groups were intraperitoneally injected with 20μg of ovalbumin and 2mg of suspension of aluminium hydroxide adjuvant into each mouse on the 0th,14 th,28th,and42 nd days of the experiment to perform asthma sensitization experiments.On the 21 st day,1% ovalbumin solution was inhaled through atomization to Cond-uct an asthma challenge experiment with 30 minutes per time and 3 times per week,also the challenge lasted until the 46 th day which could create a mouse model of asthma airway remodeling.The blank group was given equal volume of normal saline instead of ovalbumin for intraperitoneal injection and aerosol inhalation.On the 21 st day,the mice in the peiyuan asthma-reliving decoction group were given peiyuan asthma-reliving decoction(18.75 g/kg)by gavage,the blank group and the model group were given equal volumes of normal saline by gavage,and the budesonide group was given 0.26 mg/kg by atomization(1mg of budesonide mixed with 2ml of 0.9% sodium chlorideinjec-tion),then lasted for 4 consecutive weeks with 30 minutes per time and once per day.After 4 weeks,the state and pathological changes of lung tissue on asthma mice in each group were observed by using HE staining and Masson staining;the bronchial WAm/Pbm and WAt/Pbm values were measured by airway morphology;the expression levels of IL-4,IL-5,IL-13,and IL-33 in BALF were detected by ELISA,also the expression levels of IL-33 protein and ST2 L protein in lung tissue were detected by Western blot.Results:1.The resultsof HE staining showed that there was no significant patholo-gical change in the lung tissue of the blank group mice;but the epithelial cells were shed in the model group that a large number of inflammatory cell infiltration accompanied,smooth muscle cells were significantly proliferative,airway wall was significantly thickened,even lumen was narrowed compared with the blank group;the above pathological changes in the budesonide group and the peiyuan asthma-reliving decoction group were alleviated compared with the model group,while the reduction in the budesonide group was more significant.2.The results of Masson staining showed that there were no significant pathological changes in the lung tissue of the blank group mice;but collagen deposition increased in the lung tissue of the model group mice that fibrosis accompanied and mainly distributed around the airways,even the pulmonary septum thickened compared with the blank group;the above pathological changes in the lung tissue of mice in the budesonide group and peiyuan asthma-reliving decoction group were alleviated compared with the model group,while the reduction in the budesonide group was more significant.3.The results of airway morphology test showed that there was no obviou-s change in mice in the blank group;the smooth muscle layer thickness and bronchial wall thickness of mice in the model group increased significantly compared with the blank group(P<0.05),while the smooth muscle layer thickness and bronchial wall thickness of mice in budesonide group and peiyuan asthma-reliving decoction group were significantly reduced compared with the model group(P<0.05),but the thickness increased compared with the blank group(P<0.05).There was no significant comparison between budesonide group and peiyuan asthma-reliving decoction group(P>0.05).4.The results of ELISA method showed that the contents of IL-4,IL-5,IL-13 and IL-33 in the alveolar lavage solution of mice in the model group increased significantly compared with the blank group(P<0.05);while the contents of IL-4,IL-5,IL-13 and IL-33 in alveolar lavage solution in budeson-ide group and peiyuan asthma-reliving decoction group were significantly reduced compared with the model group(P<0.05),but the contents were higher than that in blank group(P<0.05).There was no significant comparison betwe-en budesonide group and peiyuan asthma-reliving decoction group(P>0.05).5.The results of Western blot method showed that the expression of IL-33 protein and ST2 L protein in the lung tissue of mice in the model group was significantly increased compared with the blank group(P<0.05),while the expression of IL-33 protein and ST2 L protein in lung tissue of budesonide group and peiyuan asthma-reliving decoction group was significantly reduced compared with the model group(P<0.05),but the expression was higher than that in blank group(P<0.05).There was no significant comparison between budesonide group and peiyuan asthma-reliving decoction group(P>0.05).Conclusions:1.Peiyuan asthma-reliving decoction can reduce the pathological chang-es of airway inflammatory cell infiltration,epithelial cell shedding,collagen deposition,smooth muscle layer thickening and airway wall thickening in asthmatic mice.2.Peiyuan asthma-reliving decoction can reduce the expression of IL-4,IL-5,IL-13 and IL-33 in BALF of asthmatic mice.3.Peiyuan asthma-reliving decoction can reduce the expression of IL-33 protein and ST2 L protein in lung tissue of asthmatic mice.4.Peiyuan asthma-reliving decoction can inhibit the production of Th2-type cytokines that created by immune cells and improve airway remodeling by inhibiting the activation of IL-33/ST2 L signaling pathway.