Targeted Blocking The β-catenin Pathway In Airway Remodeling Effects

Objective:Using Ovalbumin to establish the model of rat asthma airway remodeling, and then treated with budesonide or ICG001, observing the effect of ICG001 in airway remodeling and exploring the therapeutic effects and mechanism of the blockers ICG001 on airway remodeling in rats.Methods:Forty male Wistar rats were randomly divided into 4 groups of control(A),asthma(B), budesonide(C), and ICG001(D)(n=10 each). Using OVA to sensitize these rats to develop the asthma remodeling phase except for the group of control. That is to say, these rats in the group of asthma and treatments were sensitized with 10%OVA intraperitoneal injection at the 1stand 8thday, and then triggered with 1%OVA ultrasonic atomization from the 15 th to the 56 th day. An intraperitoneal injection of ICG001 5mg/kg for the ICG001 group at half an hour preatomization and an inhalation of budesonide2 mg for the budesonide group at 2 hours preatomization. The control rats received an aerosol inhalation saline instead of ovalbum. Specimens were collected at 24 hours after the last ultrasonic atomization. And then total cell and eosinophil cell counts in the bronchoalveolar lavage fluid(BALF) were detected. In addiation to observe the airway morphological changes and analyze the degree of airway remodeling with Image-pro plus computer graphics. The levels of transforming growth factor β1(TGF-β1) in BALF and serum were detected by ELISA. Detected the expressions of E-cadherin 、 α-smoothmuscle actin(α-SMA)、fibronectin(Fn) in lung tissue by SABC.Results:Total cell and eosinophil cell counts in BALF in Group B were more than the Group A((17.89±0.70)×10、(3.73±0.28)×109vs(1.29±0.05)×109、(0)×109); as the same result of the thickness of airway wall and smooth muscle. In Group B the levels of TGF-β1 in both BALF and serum((20.88±0.37)、(70.58±0.39) vs(1.06±0.05)、(23.67±0.30) μg/L) were observely higher; the expression of E-cadherin((0.26±0.01) vs(0.47±0.12)) was significantly decreased,while α-SMA and Fn were significantly increased((0.52±0.03)、(0.53±0.02) vs(0.37±0.08)、(0.39±0.20))(all P<0.01). In Group C and D, total cell and eosinophil cell counts in BALF were respectively [(10.97±0.36)、(10.27±0.30)×109] and[(1.10±0.35)、(1.04±0.03)×109], the thickness of airway wall and smooth muscle were respectively [(35.34±0.33)、(31.91±1.61) and(18.57±0.67)、(16.18±0.84)μm], the levels of TGF-β1 in both BALF and serum were [(3.11±0.05)、(3.07±0.05) and(31.12±0.50)、(30.72±0.47)ug/L], which were significantly decreased compared with Group B, as the same result of the expressions of α-SMA, Fn [(0.44±0.27)、(0.43±0.45) and(0.46±0.03)、(0.46±0.06)]; but the expression of E-cadherin [(0.30±0.01) 、(0.32±0.21)] was significantly increased(all P<0.01).Conclusions:1、The increased secretion of TGF-β1 induced by asthmatic chronic inflammation,occuring epithelial-mesenchymal transition, which is critical for the asthmatic airway remodeling.2、ICG001 can reduce asthmatic airway remodeling and plays a therapeutic role by blocking the signal pathway of β-catenin in the cytoplasm.