[Dynamic changes in airway hyperresponsiveness as a result of allergen and therapeutic effects of budesonide in rats].
OBJECTIVE
To investigate the dynamic changes in airway hyperresponsiveness (AHR) in allergen-induced asthma in rats and the effects of budesonide.


METHODS
Among 36 BALB/c female mice, 6 were randomized as negative control group (group C), the remaining mice were challenged with ovalbumin (OVA) to reproduce asthma. Kinetics of airway AHR of OVA-induced asthmatic mice was carried out as follows: on day 15, 18, 21 and 25 (A1, A2, A3, A4 groups), 6 mice were randomly chosen and sacrificed after measurement of airway AHR to investigate tidal volume (V(T)), airway resistance of expiring phase (R(A)), compliance of thorax and lung (C(T-L)) with different doses of methacholine chloride (MCH). In group B 6 mice were randomly chosen and treated with 1 mg budesonide aerosol once per day from day 15 to 17, then sacrificed on day 18. Their physiological and pathological changes were determined similarly to those of A2 group.


RESULTS
(1) The increase of R(A) in group A1, A2 and A3 were significantly higher than that in group C when MCH reached the dose of 200 ng/g. (2) The decrease of C(T-L) in group A1 and A2 was significant with 100 ng/g and 200 ng/g MCH. (3) The value of V(T) markedly decreased in group A2 with 100 ng/g MCH and in all asthma model groups with 200 ng/g MCH than that in group C. (4) There was an eosinophil-dominant inflammatory infiltration in the asthma lungs, and the degree of infiltration peaked on day 15, and then alleviated afterwards. (5) With the dose of 200 ng/g MCH, the increase of R(A) in group B was significantly alleviated when compared with that in group A2, but there was no significant difference between group B and C. With the dose of 100 and 200 ng/g MCH, the decrease of C(T-L) in group B was significantly less marked compared with that in group A2 but there was no significant difference between group B and group C; the decrease of V(T) in group B was significantly lessened in degree when compared with that in group A2, while there was no statistical difference between group B and group C. The infiltration of inflammatory cells was obviously alleviated and the repair of airway epithelium was better in budesonide group.


CONCLUSIONS
(1) Airway hyperresponsiveness increases greatly in mice challenged and sensitized with OVA, and it lasts for about 7 days and then declines afterwards. (2) Budesonide aerosol could effectively alleviate the eosinophil dominant inflammatory response and decrease AHR in the murine asthma model.
Gong
Pi-hua
PH
Department of Respiratory Medicine, Peking University, People's Hospital, Beijing 100044, China.
Gao
Zhan-cheng
ZC
Hu
Ping
P
Dong
Jian-qiang
JQ
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D019819:Budesonide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation
D000485:Allergens; D019819:Budesonide