Investigation of the measurement of murine airway hyperres- ponsiveness and the therapeutic effects of budesonide on ovalbumin sensitized and challenged mice

摘要

Background Airway hyperresponsiveness (AHR) is one of the most important characteristics of asthma. This study investigated the parameters, by which assess the airway responsiveness under tidal ventilation. Methods Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) (group A) , and part of them were treated with budesonide aerosol (group B). All the mice were anaesthetized and mechanically ventilated. The values of tidal volume (V_t) , airway pressure (P_A) , airway flow (F) , expiratory lung resistance ( R_L) and dynamic compliance of the thorax and lung (C_(T-L)) were recorded by the AniRes2003 animal lung function system. In addition, the expiratory volume in the first 0.1 second after the start of expiration (EV_(0.1)) was obtained according to the flow-volume (F-V) curve. The maximal or minimal values of EV_(0.1), R_L and C_(T-L) were documented after each dose of methacholine ( MCH) and compared with values from negative control group (group C ). Results (1) When the dose of MCH reached 100 ng/g or 200 ng/g, the decrease of V_t in group A was much more significant than group C (P =0.001, <0.001 respectively) , but not so between groups B and group C (P = 0.974, 0.362 respectively). (2) With the dose of 25, 50, 100 or 200 ng/g MCH, the decrease in percentage of EV_(0.1) in group A was much higher than group C (P - 0.012, 0.025, 0.001, 0.003 respectively) , while that in group B showed no significant difference as compared with group C ( P = 0.507, 0.896, 0.972, 0.785). (3) R_L and C_(T-L): with the dose of 200 ng/g MCH, there was a statistically significant increase of R_L in group A compared to group B or group C ( P < 0.001, < 0.001 respectively) , but no significant difference between groups B and C (P =0.266). With doses of 100 ng/g and 200 ng/g MCH, there was a statistically significant decrease of C_(T-L) in group A compared to group B (P =0.001, = 0.001) and group C (P< 0.001, < 0.001 respectively) , but no significant difference between groups B and C (P =0.775, 0.310). (4) Histopathology; there were eosinophilic predominant peribronchial and perivascular inflammatory influx in murine lungs after OVA sensitizing and challenging, which could be counteracted by inhalation of budesonide in group B. Conclusions The decline in EV_(0.1) in response to MCH challenge correlated with simultaneous changes in V_t, R_L and C_(T-L), but more sensitively than all the other parameters. The decline in EV_(0.1) and inflammation in murine lung could be significantly alleviated by inhalation of nebulized budesonide solution, which indicated that EV_(0.1) to MCH is a valid measure of AHR in mice.