Mucus Hypersecretion In The Airway Of Sensitized Rats: The Effects Of EGFR Pathway And A Novel Therapeutic Intervention.

Objective: To explore the production of mucus hypersecretion and the relationship between the mucus hypersecretion and Epidermal Growth Factor Receptor (EGFR), and to use selective inhibitors of EGFR: tyrosine kinase block as a novel therapeutic intervention.Method: According to the method of factorial design, all the rats underwent two factors: M factor, including three levels, saline control, asthma and genistein treatment; T factor, including four levels, 1th day,3th day,7th day and 15th day, when the first challenge time was considered as zero. 48 wistar rats were randomly divided into twelve groups, and every group consisted of four rats. GCH/M index (the number of goblet cells per mm in bronchial epithelia) was detected by sequential alcian blue (AB) and periodic acid-Schiff (PAS) staining of airway tissue. Both MUC5AC and EGFR proteins were located in bronchpulmonary tissues using immunohistochemical analysis. Serum TGF-αlevel was detected with radioimmunoassay.Results: (1) There were the goblet cell hyperplasia of bronchial epithelia, lots of mucus products in bronchial lumen and the mucus plugs in bronchiole in asthma group, but there were a little mucus products and no mucus plug in both control group and treatment group, (2) Asthma rats had higher MUC5AC protein expression and GCH/M index than those in both control group and treatment group. (3) the result of factorial analysis showed that the rats in the different models had different MUC5AC protein expression and GCH/M index in airway epithelia (F=10.41 p<0.01,F=3388.49 p<0.01), and there were different EGFR expression in brochial epithelium and different serum TGF-αlevel in different models (F=610.85 P<0.01,F=57.54 P<0.01).The results of interactions showed that there were no significant difference among different time in the control group(F=3.05,0.92,0.16,0.41;P>0.05), however, there were significant differences among different time in asthma group and genistein treatment group in MUC5AC expression, GCH/M index, EGFR protein expression and serum TGF-α: (F=2.17,993.53;P<0.01)(F=0.23 P<0.01;F=96.30 P<0.05)(F=127.36,10.84;P<0.01)(F=23.59 P<0.01;F=3.70 P<0.05).Compared with different little groups: MUC5AC expression in asthma group were significant higher than that in control group at 7th day and 15th day (t=3.68 p<0.01,t=2.54 p<0.01); But MUC5AC expression had no difference between control and treatment group at 7th and 15th day (t=0.83 p=0.41,t=0.94 p=0.35). (4) There were significant positive correlations between MUC5AC expression and GCH/M index (r=0.983...