[Changes of airway smooth muscle cell apoptosis in asthmatic airway remodeling and the effect of dexamethasone in rats].Zhonghua Jie He He Hu Xi Za Zhi. 2008 Aug; 31(8):607-10.ZJ
To observe the changes of airway smooth muscle cells (ASMC) apoptosis in the airway remodeling process of asthma, and to evaluate the effect of dexamethasone on ASMC apoptosis and the possible mechanisms.
Thirty six male Sprague-Dawley rats were randomly divided into 3 groups, including a control group, an asthma group and a dexamethasone treated group. The rats were sensitized with ovalbumin and Al(OH)(3), and repeatedly exposed to aerosolized ovalbumin. ASMC apoptosis was measured by the technique of TdT-mediated dUTP-biotin nick end labeling (TUNEL). Bcl-2 protein and mRNA, and Bax protein and mRNA in airway smooth muscles were measured by immunohistochemistry and in situ hybridization respectively. SPSS version 11.5 was used for statistical analysis. Data were presented as ((-x) +/- s), and means were compared with analysis of variance. The correlation of two variables was analysed by linear correlation analysis.
The apoptosis index (AI) of ASMC was separately 0.201 +/- 0.022, 0.030 +/- 0.016, 0.118 +/- 0.043 in the control, the asthma, and the dexamethasone asthma, treated group. Immunohistochemistry showed that the expression of Bcl-2 protein (A) in airway smooth muscles in above groups was 0.060 +/- 0.012, 0.112 +/- 0.028 0.080 +/- 0.010. In situ hybridization showed that the level of Bcl-2 mRNA in airway smooth muscles in the control, the asthma, and the dexamethasone treated group was 0.065 +/- 0.019, 0.157 +/- 0.019 and 0.099 +/- 0.029. The expression of Bax protein in each group was 0.120 +/- 0.020, 0.062 +/- 0.012 and 0.093 +/- 0.010 respectively. Accordingly the level of Bax mRNA in each group was 0.155 +/- 0.025, 0.074 +/- 0.019 and 0.118 +/- 0.031 respectively. The AI of ASMC was negatively correlated with Wam/Pbm (r = -0.860, P < 0.01) and the relative content of Bcl-2 protein (r = -0.783, P < 0.01), but was positively correlated with the relative content of Bax protein (r = 0.873, P < 0.01).
The reduction of ASMC apoptosis may participate in the remodeling process of asthma. Dexamethasone induces ASMC apoptosis possibly by the increase of Bax expression and the decrease of Bcl-2 expression in airway smooth muscles.