白三烯受体拮抗剂对哮喘小鼠气道重塑及细胞周期蛋白D1的表达影响  

Effect of leukotrine receptor antagonist on airway remodeling and the expression of cyclin D1 in a murine model of asthma

作　　者：葛海燕[1] 黄茂[1] 姚欣[1] 殷凯生[1] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2006年第4期257-261,F0003,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：南京医科大学科技创新基金资助项目(CX2004011)

摘　　要：目的:研究应用白三烯受体拮抗剂(孟鲁司特钠)对哮喘小鼠肺组织中细胞周期蛋白D1(CyclinD1)的表达影响及对支气管哮喘气道重塑的作用,探讨白三烯受体拮抗剂在哮喘治疗中的作用。方法:将30只BALB/c小鼠随机分为正常对照组、哮喘组、孟鲁司特钠组3组,每组10只;卵蛋白致敏和激发建立哮喘小鼠模型;HE染色观察各组气道炎症发生及气道结构改变情况;免疫组化观察肺组织中CyclinD1的表达及定位;RT-PCR及Western-blot测定各组小鼠肺组织中CyclinD1的mRNA和蛋白表达变化。结果:HE染色提示哮喘组与对照组相比出现嗜酸性粒细胞浸润增多、纤毛脱失、平滑肌细胞层增厚等改变,而治疗组上述改变较哮喘组为轻;免疫组化显示CyclinD1在哮喘小鼠气道平滑肌细胞、内皮细胞、成纤维细胞中皆有表达而在对照组中表达减弱(P<0.05),而治疗组表达量较哮喘组低(P<0.05);RT-PCR及Westernblot检测发现CyclinD1在哮喘组表达较对照组为高(P<0.01),而治疗组表达量低于哮喘组(P<0.01)。结论:哮喘小鼠肺组织中CyclinD1表达量较正常组为高;白三烯受体拮抗剂能够抑制CyclinD1表达,减轻气道炎症反应、延缓气道重塑进程。Objective： To investigate the influence of the leukotriene receptor antagonist （montelukast） on airway remodeling and the expression of cyclin D1 in a routine model of asthma, and to explore the role of montelukast in dealing with asthma. Methods： Mice were sensitized and challenged with ovalbumin to establish the asthmatic model. The characteristic airway inflammation and alteration of airway structure were detected by HE staining. Pulmonary expression and location of cyclinD1 were examined by immunohistochemistry. The expression of cyclinD1 in both mRNA and protein level was detected by RT-PCR and western blot, respectively. Results： Eosinophile infiltration, cilium loss, smooth muscle cell layer thickening were decreased in therapeutic group than those in the asthmatic group. There was more cyclin D1 staining in smooth muscle cell, endothelium cells, fibroblast in asthmatic group than those in the normal group （P 〈 0.05）, and they were decreased in the therapeutic group （P 〈 0.05）. The mRNA and protein expression level of cyclin D1 in asthmatic group was higher than that in the normal group （P 〈 0.01）, and they were decreased in therapeutic group （P 〈 0.01）. Conclusion： The expression of cyclin D1 in asthmatic group is higher than that in the normal group, and leukotriene receptor antagonist could inhibit cyclin D1 expression, thus relieve airway inflammation and delay the process of airway remodelding.

关 键 词：支气管哮喘 气道重塑 白三烯受体拈抗剂 细胞周期蛋白D1 

分 类 号：R562.25[医药卫生—呼吸系统]