Experimental Study On The Effect Of Blocking ?-catenin Signaling Pathway On Airway Remodeling In Asthma

Objective:The effect and the related mechanism of blocking ?-catenin pathway on asthma airway remodeling was observed by blocking the ?-catenin signaling pathway with ICG001.Methods:8-week-old SPF male Wistar rats were randomly divided into four groups of 10,control group(group A),asthma group(group B),budesonide group(group C),ICG001group(group D).The airway remodeling model was established by ovalbumin(OVA)sensitization.Rats in group A received the same dose of saline every time.Rats in group B,C and D were sensitized to d1 and d8,d15 began to stimulate,20min/d,for 8 weeks;group C was inhaled budesonide 2mg two hours before each challenge;group D was injected ICG001 5mg/kg intraperitoneal the first half hour.Rats in each group were collected for lung tissue 24 hours after the last challenge.HE staining was used to observe the general and pathological condition of lung tissue.The thickness of bronchial wall and smooth muscle were measured by BI2000 analysis system.The expression of Snail and MMP-7 in lung tissue was detected by real-time fluorescent quantitative PCR.Results:Behavioral observation,group B rats were messy,decreased activity,weight loss,as a whole.After each challenge,group B appeared varying degrees of standing hair,screaming,shortness of breath,lips cyanosis and so on.The above performance was notobvious in group C and D.Group A did not show the above.General observation showed the lung tissue in group B was surface irregular,colors muddy,uneven expansion and had irregular dark red congestion zone.The changes of group C and D were mild,but there was no change in group A.HE staining showed that group A was normal without smooth muscle thickening and inflammatory cell infiltration.Group B showed bronchial wall and smooth muscle thicken,luminal narrow,and a large number of inflammatory cell infiltration.Group C and D were significantly improved compared with group B.Measurement of bronchial wall and smooth muscle thickness showed that group B bronchial wall,smooth muscle thickness [(43.22 ± 1.36)and(21.78 ± 0.84)?m] were significantly higher than those in group A [(26.32 ± 0.24)and(14.21 ± 0.13)?m],respectively.The group C and D [(36.51 ± 0.44),(19.67 ± 0.92)?m,(32.69 ± 1.57),(17.39 ± 0.91)?m] were significantly lower than those in group B(all P <0.01).The expression of Snail and MMP-7 in lung tissue was detected by real-time fluorescent quantitative PCR,the expression of Snail and MMP-7 was the highest in group B,group was higher than group A,and group D was significantly lower(all P <0.01).Conclusion:1.ICG001 can block the ?-catenin signaling pathway to reverse asthma airway remodeling.2.ICG001 blocking ?-catenin signaling pathway by inhibiting downstream expression of Snail and MMP-7 to reverse asthma airway remodeling.