caveolin-1和p42/p44MAPK在哮喘大鼠气道重塑中的作用及罗红霉素对其表达的影响

The role of caveolin-1 and p42/p44MAPK in the airway remodeling of asthmatic rats and the influence of roxithromycin on its expression

目的:探讨caveolin-1、p42/p44MAPK在哮喘大鼠气道重塑中的作用及罗红霉素对其的干预作用。方法:SPF级雄性SD级大鼠32只,随机分为对照组(C组)、哮喘组(A组)、地塞米松组(D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,图像分析软件测定支气管壁厚度和支气管平滑肌层厚度,Western blot法测定支气管平滑肌层caveolin-1、p-p42/p44MAPK蛋白相对含量。结果:A组大鼠支气管管壁总面积(Wat)/支气管基底膜周径(Pbm)、支气管平滑肌面积(Wam)/Pbm大于C组(P<0.01),D组、R组大鼠Wat/Pbm、Wam/Pbm小于A组(P<0.01),大于C组(P<0.01);A组caveolin-1表达量显著低于C组(P<0.01),D、R两组表达高于A组(P<0.01),但低于C组(P<0.05);A组p-p42/p44MAPK表达量显著高于C组(P<0.01),D、R两组表达低于A组(P<0.01),但高于C组(P<0.01);caveolin-1表达与大鼠Wam/Pbm呈负相关(r=-0.893,P<0.01);p-p42/p44MAPK表达与大鼠Wam/Pbm呈正相关(r=0.918,P<0.01);caveolin-1与p-p42/p44MAPK表达呈负相关(r=-0.873,P<0.01)。结论:caveolin-1与p42/p44MAPK通路在哮喘大鼠气道重塑中可能存在一定的内在联系,罗红霉素可能部分通过对两者之间的影响而发挥其抑制哮喘气道平滑肌重塑的作用。

Objective： To explore the role of caveolin-1 and p42/p44MAPK in the airway remodeling of asthmatic rats and the intervention of Roxithromycin. Methods： Thirty-two healthy, male Sprague-Dawley rats were randomly divided into four groups averagely： control group （group C）, asthmatic group （group A）, Dexametha- sone group （group D） and Roxithromycin group （group R ）. Asthmatic rats model was duplicated by the sensitization and provocation with ovalbumin. The total bronchial wall thickness （Wat/Pbm） and the bronchial smooth muscle thickness （Wam/Pbm） were measured with image -pro plus 6.0. The protein expressions of caveolin-1 and p-p42/ p44MAPK in the airway smooth muscle were measured with Western blot. Results： Wat/Pbm, Wam/Pbm of group A were significantly higher than those of group C （P〈0.01）, those of group D and group R were lower than those of group A （P〈0.01）, nevertheless, higher than those of group C （P〈0.05）. The expression of caveolin-1 in group A was significantly lower than that of group C （P〈0.01）, that of group D and group R were significantly higher than that of group A （P〈0.01）, but decreased compared with group C （P〈0.05）; the expression of p-p42/p44MAPK in group A significantly increased compared with group C （P〈0.01）, that of group D and group R were significantly decreased than that of group A （P〈0.01）, but still increased compared with group C （P〈0.01）. There were significantly negative correlation between Wam/Pbm and the protein expression of caveolin-1 （r=-0.893, P〈0.01）. There weresignificantly positive correlation between Wam/Pbm and the expression of p-p42/p44MAPK measured with West- ern blot （r=-0.918, P〈0.01）. There was significantly negative correlation between the expressions of caveolin-1 and p-p42/p44MAPK measured with Western blot （r= -0.873, P〈0.01）. Conclusions： There may be some connec- tions between caveolin-1 and p42/p44MAPK signaling in airway remodeling of asthmatic rats, and Roxithromycin maybe inhibits airway remodeling partly through caveolin-1 and p42/p44 MAPK signaling pathway.