The Effects Of Dll4-Notch3 Signaling On Airway Inflammation And Airway Remodeling In Asthmatic Rats

Objective: To study the effects of Dll4-Notch3 signaling on airway inflammation and airway remodeling in asthmatic rats.Methods: SPF grade,female SD rats were selected,Atomization inhalation of OVA and using Dll4,Notch3 antibodies in vivo intervention to make asthma model.After the asthmatic model was successful,the airway pressure was measured in each group.The infiltration of eosinophils(EOS)in the airway wall was analyzed by image analysis software in HE.To measured the circumference of bronchial lumen,the wall area,the area of bronchial smooth muscle and the number of smooth muscle cells,At the same time,measured the migration of airway smooth muscle to airway epithelium.The expression of PCNA,Bcl-2 and Notch3 in airway smooth muscle cells of rats in each group were observed by immunohistochemical method(IHC),and the expression of Dll4 in airway epithelial cells was observed.Real time quantitative PCR(RT-q PCR)and Western-blot were used to detect the expression of m RNA and protein of Dll4 and Notch3 in lung tissues of rats in each group.Results:(1)?The airway responsiveness,the number of EOS infiltration in the airway wall,and the wall thickness of the airway was significantly higher in asthmaic 1 weeks and asthmaic 4 weeks than control group(P<0.05),In addition,compared with asthmatic 1 weeks,the above indicators in asthmatic 4 weeks were significantly increased(P<0.05).?Compared with control group,the distance between the smooth muscle and the basement membrane was decreased in asthmaic 1 weeks and asthmaic 4 weeks(P<0.05);the asthmaic 4 weeks was decreased than asthmaic 1 weeks(P<0.05).?The expression of Notch3 and Dll4 m RNA in asthmaic 1 weeks and asthmatic 4 weeks were higher than control group(P<0.05);There was significant difference between them(P<0.05).Western-blot and IHC test results consistent with the RT-q PCR.(2)?The airway reactivity,the number of EOS infiltration in the airway wall,and the wall thickness of the bronchial wall in asthmatic 1 weeks and asthmatic 4 weeks were higher than control group(P<0.05),the above indicators of asthmatic 4 weeks were higher than asthmatic 1 weeks(P<0.05).The above indicators in Notch3 treatment 1 weeks and Notch3 treatment 4 weeks were higher than control group(P<0.05),the above indicators of Notch3 treatment 4 weeks were higher than Notch3 treatment 1 weeks(P<0.05).The above indicators in Dll4 treatment 1 weeks and Dll4 treatment 4 weeks were higher than control group(P<0.05),the above indicators in Dll4 treatment 4 weeks were higher than Dll4 treatment 1 weeks(P<0.05).In addition,compared with Notch3 treatment 1 weeks and Notch3 treatment 4 weeks,the above indicators in asthmatic 4 weeks were significantly increased(P<0.05),the above indicators in asthmatic 4 weeks were higher than Dll4 treatment 4 weeks,but there was no significant difference between them(P>0.05).?The distance between the smooth muscle and the basement membrane in asthmatic 1 weeks and asthmatic 4 weeks were lower than control group(P<0.05),the above indicators of asthmatic 4 weeks were lower than asthmatic 1 weeks(P<0.05).The above indicators in Notch3 treatment 1 weeks and Notch3 treatment 4 weeks were lower than control group (P<0.05),The above indicators of Notch3 treatment 4 weeks were lower than Notch3 treatment 1 weeks(P<0.05).The above indicators in Dll4 treatment 1 weeks and Dll4 treatment 4 weeks were lower than control group(P<0.05),the above indicators in Dll4 treatment 4 weeks were lower than Dll4 treatment 1 weeks(P<0.05).In addition,compared with Notch3 treatment 1 weeks and Notch3 treatment 4 weeks,the above indicators in asthmatic 4 weeks were significantly decreased(P<0.05),the above indicators in asthmatic 4 weeks were higher than Dll4 treatment 4 weeks,but there was no significant difference between them(P>0.05).?The expression of Notch3 and Dll4 m RNA in asthmaic 1 weeks and asthmatic 4 weeks were higher than control group(P<0.05),meanwhile,there was significant difference between them.The above indicators in Notch3 treatment 1 weeks and Notch3 treatment 4 weeks were higher than control group(P<0.05),the above indicators of Notch3 treatment 4 weeks were higher than Notch3 treatment 1 weeks(P<0.05).The above indicators in Dll4 treatment 1 weeks and Dll4 treatment 4 weeks were higher than control group(P<0.05),the above indicators in Dll4 treatment 4 weeks were higher than Dll4 treatment 1 weeks(P<0.05).In addition,compared with Notch3 treatment 1 weeks and Notch3 treatment 4 weeks,the above indicators in asthmatic 4 weeks were significantly increased(P<0.05),the above indicators in asthmatic 4 weeks were higher than Dll4 treatment 4 weeks,but there was no significant difference between them(P>0.05).Western-blot and IHC test results consistent with the RT-q PCR.Conclusions: Dll4 has specific expression in airway epithelial cells of asthmatic rats,and Notch3 is highly expressed in the whole lung tissues of asthmatic rats.Inhibition of Dll4-Notch3 signaling can improve airway inflammation and airway remodeling in asthmatic rats.These results indicate that Dll4-Notch3 signal is involved in the pathogenesis of asthma.