[Bicuculline inhibits airway remodeling in a murine model of chronic asthma].
OBJECTIVE
To investigate the effect of bicuculline, a selective GABAA receptor antagonist, on airway remodeling in the murine model of chronic allergen-induced asthma.


METHODS
Forty BALB/C mice were randomized into 4 groups, namely the control group, asthmatic model (induced by ovalbumin sensitization and challenge) group, budesonide inhalation group and bicuculline inhalation group. The mice were sacrificed 24 h after the last ovalbumin inhalation, and the lungs were lavaged with PBS and the total cells, eosinophils and lymphocytes counts were examined. Periodic acid-Schiff (PAS) staining was used for counting mucin-positive goblet cells in the lung tissue, and Masson Trichrome staining was used to evaluate collagen deposition. GABAARbeta2 and VEGF were quantified by immunohistochemistry.


RESULTS
The numbers of the total cells, eosinophils and lymphocytes counts in BALF were significantly greater in the bicuculline group than in the control and budesonide groups (P<0.01), but comparable to those in the asthmatic model group (P>0.05). The airway collagen deposition in the bicuculline group was comparable to that in the control and budesonide group (P>0.05), but was significantly less than that in the asthmatic model group (P<0.05). Significant differences were found in the airway histological mucus index between the bicuculline group and the other 3 groups (P<0.05). The airway GABAARbeta2-positive cell percentage in the bicuculline group was significantly greater that those in the control and budesonide (P<0.01 and 0.05), but similar with that in the asthmatic model group (P>0.05). The percentage of pulmonary perivascular VEGF-positive cells in the bicuculline group was significantly greater in the control and budesonide groups (P<0.01 and P<0.05), but comparable to that in the asthmatic model group (P>0.05).


CONCLUSIONS
GABAARbeta2 is expressed in both the airway epithelium and smooth muscles. Bicuculline inhalation can effectively suppress collagen deposition with a stronger inhibitory effect on mucus hypersecretion than budesonide.
Zhu
Tao
T
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. taosen66@tom.com
Ren
Xu-bing
XB
Zhu
Jing
J
Bo
Hong
H
Liu
Chun-tao
CT
D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology*; D001640:Bicuculline / Q000627:therapeutic use*; D004195:Disease Models, Animal; D058787:GABA-A Receptor Antagonists / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D058787:GABA-A Receptor Antagonists; D001640:Bicuculline