[Investigation of effect of bicuculline on expression of alpha-smooth muscle actin and airway remodeling in asthmatic mice].
OBJECTIVE
To observe the effect of bicuculline, which is a selective GABA receptor antagonist on expression of alpha-SMA in the lung tissue of rats with chronic asthma, to explore the role of the bicuculline on the airway remodeling in asthmatic mice.


METHODS
Forty BALB/c mice were randomly divided into four groups: the control group (A), the asthma model group (B), the bicuculline group (C) and bicuculline with budesonide group (D). The asthmatic model was established by sensitization and challenge with ovalbumin. The expression of alpha-SMA in the lung tissue and the thickness of the airways of mice was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining.


RESULTS
There was little expression of alpha-SMA in the lung tissue of normal mice compared with the asthma model group (P < 0.05). The expressions of alpha-SMA in the group C and D decreased compared with that in group B (P < 0.01), but no significant difference (P > 0.05) was observed between group C and D. The WAt/Pbm, WAi/Pbm, and WAm/Pbm were significantly increased in the asthma group compared with that in normal group (P < 0.05), and the WAt/Pbm, WAi/Pbm, and WAm/Pbm were decrased in the group compared with that of group B (P < 0. 01), the wAm/Pbm was decreased in the group C (P < 0. 05).


CONCLUSIONS
Over expression of alpha-SMA in asthmatic lung tissue is closely related to the onset of asthmatic. GABAAR antagonist bicuculline could inhibit the expression of alpha-SMA and alpha-SMA mRNA and alleviate airway remodeling with equivalent potency of inhaled corticosteroid. Our data suggest that GABAAR involve in the pathogenesis of asthmatic airway remodeling by upregulating the expression of alpha-SMA inducing the airway smooth muscle constriction and hyperplasia.
Ren
Xu-Bin
XB
Department of Respiratory Medicine, Division of Pulmonary Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
Liu
Chun-Tao
CT
Zhu
Tao
T
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
C558396:Acta2 protein, mouse; D000199:Actins; D058787:GABA-A Receptor Antagonists; D001640:Bicuculline