哮喘大鼠气道平滑肌细胞caveolae的变化及罗红霉素的调控作用

目的观察支气管哮喘（简称哮喘）大鼠气道平滑肌细胞微囊（caveolae）及微囊蛋白一1（caveolin一1）的表达变化，并探讨罗红霉素对其表达的影响。方法SPF级雄性SD大鼠24只，采用数学表法随机分为对照组（c组）、哮喘组（A组）、罗红霉素组（R组），每组8只。以卵白蛋白致敏和激发的方法复制大鼠哮喘气道重塑模型，图像分析软件测定气道壁厚度（Wat／Pbm）及气道平滑肌层厚度（Wam／Pbm）；透射电镜观察eaveolae超微结构；Westernblot法测定caveolin—l的表达变化。结果（1）A组大鼠Wat／Pbm、Wam／Pbm大于C组（P〈0．01）；R组大鼠Wat／Pbm、Wam／Pbm小于A组（P〈0．01），大于C组（P〈0．01）；（2）透射电镜显示c组ASMC胞膜及胞质eaveolae含量丰富、形态多样，A组caveolae含量少、结构单一，R组eaveolae含量明屁减少，但较A组多；（3）Westernblot法显示c组caveolin一1高表达，A组表达明显低于c组（P〈0．01）；R组caveolin-1表达显著高于A组（P〈0．01），但较c组表达减少；（4）caveolin-1表达与Wam／Pbm呈负相关（r=-0．928，P〈0．01）。结论哮喘大鼠气道平滑肌细胞eaveolae结构明显减少，caveolin-1表达减少，提示caveolae缺乏与哮喘气道重塑有密切关系，罗红霉素可能通过caveolae的影响而抑制哮喘气道重塑。

Effect of Roxithromycin on the Caveolae of Airway Smooth Muscle Cells in Asthmatic Rats.

Objective To observe the change of caveolae in the airway smooth muscle cells of asthmatic rats and to study the effect of Roxithromycin. Methods Twenty - four healthy,male Sprague - Dawley rats were randomly divided into three groups on average,in- cluding control group（group C） ,asthmatic group（ group A） , and Roxithromycin group（group R）. A rat asthma model was exploited, in which rats were sensitized and provoeated with ovalbumin. The total bronchial wall thickness （Wat/Pbm） and the bronchial smooth mus- cle thickness （Wam/Pbm） were measured with image - pro plus 6.0. The uhrastrueture changes of caveolae were observed by transmis- sion electron microscpe. The content of caveolin - 1 detected by Western blot. Results Wat/Pbm,Wam/Pbm of group A were significant- ly higher than those of group C （P 〈 0.01 ） ,those of group R decreased than group A （P 〈 0. O l ）, nevertheless, higher than those of group C（P 〈 0. 01 ）. In group C ,TEM showed there was abundant eaveolae in cell membrane and inside cell membrane with multiple shapes. Group A showed that there was fewer caveolae with structure destroyed. The pathological alterations of group R appeared between group C and group A. Western blot showed that the expression of caveolin - 1 in group A significantly decreased compared with group C （ P 〈 0.01 ） ,that of group R was significantly elevated than that of group A （P 〈 0.01 ） , but decreased compared with group C （P 〈 0.01 ）. There was significantly negative correlation between Wam/Pbm and the expression of caveolin - 1 detected by Western Blot （ r = - 0. 928,P 〈 0. 01 ）. Conclusion The amount of caveolae in airway smooth muscle of aslhma rats was obviously deereased, so as the expression of caveolin -1 ,which ,lemonstrated that there was close relationship between tile deficiency of eaveolae and airway remodeling of asthma. Roxithromvcin maybe inhibit airway remodeling through eaveolae.